The present invention relates to novel benzoheterocyclic derivatives having excellent vasopressin antagonistic activities, vasopressin agonistic activities and oxytocin antagonistic activities.
Various benzoheterocyclic compounds analogous to the compounds of the present invention have been known to have anti-vasopressin activities in European Patent Publication No. 0382128 (published on Aug. 15, 1990), WO 91/05549 (published on May 2, 1991), WO 91/16916 (published on Nov. 14, 1991), WO 94/08582 (published on Apr. 28, 1994), WO 94/12476 (published on Jun. 9, 1994), JP-A-5-320135 (published on Dec. 3, 1993), JP-A-6-16643 (published on Jan. 25, 1994), and JP-A-6-157480 (published on Jun. 3, 1994), among which, for example, JP-A-6-16643 discloses the following compounds. 
Some other literatures disclose various benzoheterocyclic compounds which are analogous to the compounds of the present invention in the chemical structure but are different in the pharmacological properties. For example, EP-A-294647 discloses some analogous compounds having positive inotropic action, vasodilating activity and platelet agglutination inhibiting activity, wherein the intermediate compounds of the following formula are also disclosed. 
U.S. Pat. No. 3,542,760 (issued Nov. 24, 1970), U.S. Pat. No. 3,516,987 (issued Jun. 23, 1970) and U.S. Pat. No. 3,458,498 (issued Jul. 29, 1969) disclose also the following compounds which are useful as diuretics, hypoglycemics, antibacterials or anti-convulsants. 
J. Chem. Soc. Perkin Trans., 1, 1985, pp. 1381-1385 discloses the following compounds but does not mention any pharmacological activity thereof. 
An object of the present invention is to provide a benzoheterocyclic derivative of the following formula [1]: 
wherein G is a group of the formula: 
or a group of the formula: 
R1 is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent,
R2 is a group of the formula: xe2x80x94NR4R5 (in which R4 and R5 are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: xe2x80x94(O)mxe2x80x94Axe2x80x94(CO)uNR6R7 (in which m and u are each 0 or 1, but both m and u should not be simultaneously 0, A is a lower alkylene group, R6 and R7 are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R6 and R7 may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group),
R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group,
or R2 and R3 may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group,
R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula: 
xe2x80x83(in which p is 1 or 2, R8 is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R9 is a group of the formula: xe2x80x94NR10R11 (in which R10 is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R11 is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an amino-carbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula: 
xe2x80x83a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R10 and R11 may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylamino-carbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: xe2x80x94(A)mxe2x80x94CHR12R13 (in which A is the same as defined above, R12 is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R13 is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)),
X is a methylene group, a single bond, a group of the formula: xe2x95x90CHxe2x80x94 or a group of the formula: xe2x80x94NR14xe2x80x94 (in which R14 is a hydrogen atom, a lower alkyl group or a lower alkanoyl group),
Y is a group of the formula: xe2x80x94NRA (in which RA is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: xe2x80x94ACONRBRC (in which RB and RC are the same or different and each a hydrogen atom or a lower alkyl group, or RB and RC may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)),
provided that when R2 is a group of the formula: xe2x80x94NR4R5 (in which R4 and R5 are the same or different and each a hydrogen atom, a lower alkyl group or a benzoyl group), a hydrogen atom, a hydroxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group, a lower alkoxy group, a lower alkanoyloxy-substituted lower alkyl group, a group of the formula: xe2x80x94(O)mxe2x80x94Axe2x80x94(CO)uNR6R7 (m and u are the same as defined above, R6 and R7 are the same or different and each a hydrogen atom or a lower alkyl group, or R6 and R7 may bind together with the nitrogen atom to which they bond to form a 5- to 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group), or an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; or R2 and R3 may bind together to form an oxo group or a lower alkylidene group; and when R is a group of the formula: 
xe2x80x83and R8 in said group is a hydrogen atom, a lower alkyl group, a hydroxy group, a halogen atom, a lower alkoxy group or an amino group, then R9 should not be a hydrogen atom, a phenyl-lower alkoxycarbonyl group, nor a group of the formula: xe2x80x94NR10R11 (R11 is a lower alkanoyl group or a phenoxy-lower alkanoyl group having optionally 1 to 3 substituents selected from a lower alkyl group and a lower alkoxy group on the phenyl ring), or
when R1 is a hydrogen atom, R2 is a hydrogen atom, an amino group, a mono-lower alkylamino group or a di-lower alkylamino group, or R2 and R3 may bind together to form an oxo group, then R9 should not be a phenyl group having optionally a substituent selected from a hydroxy group, a lower alkyl group, a lower alkoxy group and a lower alkanoyloxy group on the phenyl ring, or
when R9 is a group of the formula: 
(n is 1 or 2), and G is a group of the formula: 
(R2 and R3 are the same as defined above), then X should not be a methylene group nor a group of the formula:xe2x95x90CHxe2x80x94, or
when one of R10 and R11 is a hydrogen atom, the other should not be a lower alkyl group,
or a pharmaceutically acceptable salt thereof.
The present inventors have intensively studied and have found that the compounds of the formula [1] and a pharmaceutically acceptable salt thereof have excellent vasopressin antagonistic activities, vasopressin agonistic activities and excellent oxytocin antagonistic activities.
The compounds of the formula [1] of the present invention and a pharmaceutically acceptable salt thereof show excellent vasopressin antagonistic activity, for example, vasodilating activity, hypotensive activity, activity for inhibiting saccharide release in liver, activity for inhibiting growth of mesangium cells, water diuretic activity, platelet agglutination inhibitory activity, inhibitory activity for vomiting, activity for promoting urea excretion, inhibitory activity on secretion of factor VIII, activity for promoting heart function, activity for inhibiting constriction of mesangium cells, inhibitory activity on production of saccharide in liver, inhibitory activity on aldosterone secretion, inhibitory activity on production of endotheline, regulation activity on renin secretion, memory regulation activity, thermoregulation activity, activity for regulating production of prostaglandin, and hence, they are useful as vasodilators, hypotensive agents, water diuretics, platelet agglutination inhibitors, promoters for urea excretion, agent for heart failure and, agent for renal failure, etc., and are used in the prophylaxis or treatment of hypertension, edema, ascites, heart failure, renal function disorder, vasopressin parasecretion syndrome (SIADH), hepatocirrhosis, hyponatremia, hypokalemia, diabetes, circulation disorder, motion sickness, water metabolism disorder, renal failure, various diseases associated with ischemic, and the like. Besides, the compounds of the present invention and a pharmaceutically acceptable salt thereof are characteristic in very few side effects and a prolonged action for a long time in a living body.
The compounds [1] of the present invention and a pharmaceutically acceptable salt thereof also show vasopressin agonistic activities, for example, effects on various urinary disorders, polyuria or hemostatic disorders, and hence, they are useful in the prophylaxis or treatment of pollakisuria, diabetes insipidus, urine incontinence, enuresis, especially nocturnal enuresis, spontaneous hemorrhage, hemophilia, von Willebrand""s disease, uremia, congenital and acquired platelet dysfunction, hemostatic derangement caused by surgical procedures or accidental trauma, or hepatic cirrhosis.
In addition, the compounds [1] of the present invention and a pharmaceutically acceptable salt thereof also show oxytocin antagonistic activities, for example, inhibitory effect on uterine smooth muscle constriction, inhibitory effect on milk secretion, inhibitory effect on synthesis and secretion of prostaglandin, and vasodilating activity, and hence, they are useful in the protection or treatment of oxytocin-associated diseases, especially premature delivery, dysmenorrhea, endometritis, or in stopping labor preparatory to Caesarian delivery.
The benzoheterocyclic derivatives of the formula [1] of the present invention especially include the following compounds.
(1) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a methylene group, R1 is the same as defined above in the definition for the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (in which R4 and R5 are the same as defined above in the definition for the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent on the phenyl ring and a pyridyl group on the pyridine ring.
(2) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a hydrogen atom.
(3) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a hydroxy group.
(4) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a carboxy-substituted lower alkyl group.
(5) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(6) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(7) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a lower alkanoyl group.
(8) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form an oxo group.
(9) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a lower alkylidene group.
(10) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(11) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(12) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(13) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a methylene group, R1 is the same as defined above in the definition for the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the definition for the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
R9 and p are the same as defined above, and R8 is a hydrogen atom).
(14) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a hydrogen atom.
(15) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a hydroxy group.
(16) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a carboxy-substituted lower alkyl group.
(17) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(18) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(19) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a lower alkanoyl group.
(20) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form an oxo group.
(21) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a lower alkylidene group.
(22) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(23) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(24) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(25) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
R9 and p are the same as defined above in the formula [1], and R8 is a lower alkyl group).
(26) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a hydrogen atom.
(27) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a hydroxy group.
(28) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a carboxy-substituted lower alkyl group.
(29) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(30) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(31) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a lower alkanoyl group.
(32) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form an oxo group.
(33) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a lower alkylidene group.
(34) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(35) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(36) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(37) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a hydroxy group).
(38) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a hydrogen atom.
(39) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a hydroxy group.
(40) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a carboxy-substituted lower alkyl group.
(41) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(42) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(43) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a lower alkanoyl group.
(44) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form an oxo group.
(45) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a lower alkylidene group.
(46) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(47) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(48) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(49) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a nitro group).
(50) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a hydrogen atom.
(51) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a hydroxy group.
(52) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a carboxy-substituted lower alkyl group.
(53) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(54) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(55) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a lower alkanoyl group.
(56) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form an oxo group.
(57) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a lower alkylidene group.
(58) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(59) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(60) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(61) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a halogen atom).
(62) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a hydrogen atom.
(63) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a hydroxy group.
(64) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a carboxy-substituted lower alkyl group.
(65) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(66) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(67) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a lower alkanoyl group.
(68) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form an oxo group.
(69) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a lower alkylidene group.
(70) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(71) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(72) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(73) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a lower alkoxy group).
(74) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a hydrogen atom.
(75) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a hydroxy group.
(76) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a carboxy-substituted lower alkyl group.
(77) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(78) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(79) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a lower alkanoyl group.
(80) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form an oxo group.
(81) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a lower alkylidene group.
(82) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(83) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(84) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(85) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent on the phenyl ring and a pyridyl group on the pyridine ring.
(86) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a hydrogen atom.
(87) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a hydroxy group.
(88) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a carboxy-substituted lower alkyl group.
(89) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(90) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(91) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a lower alkanoyl group.
(92) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form an oxo group.
(93) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a lower alkylidene group.
(94) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(95) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(96) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(97) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a hydrogen atom).
(98) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a hydrogen atom.
(99) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a hydroxy group.
(100) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a carboxy-substituted lower alkyl group.
(101) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(102) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(103) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a lower alkanoyl group.
(104) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form an oxo group.
(105) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a lower alkylidene group.
(106) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(107) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(108) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(109) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a lower alkyl group).
(110) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a hydrogen atom.
(111) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a hydroxy group.
(112) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a carboxy-substituted lower alkyl group.
(113) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(114) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(115) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a lower alkanoyl group.
(116) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form an oxo group.
(117) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a lower alkylidene group.
(118) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(119) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(120) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(121) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a hydroxy group).
(122) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a hydrogen atom.
(123) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a hydroxy group.
(124) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a carboxy-substituted lower alkyl group.
(125) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(126) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(127) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a lower alkanoyl group.
(128) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form an oxo group.
(129) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined. in above (121), and R2 and R3 bind together to form a lower alkylidene group.
(130) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(131) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(132) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(133) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a nitro group).
(134) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a hydrogen atom.
(135) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a hydroxy group.
(136) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a carboxy-substituted lower alkyl group.
(137) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(138) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(139) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a lower alkanoyl group.
(140) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form an oxo group.
(141) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a lower alkylidene group.
(142) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(143) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(144) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(145) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a halogen atom).
(146) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a hydrogen atom.
(147) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a hydroxy group.
(148) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a carboxy-substituted lower alkyl group.
(149) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(150) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(151) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a lower alkanoyl group.
(152) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form an oxo group.
(153) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a lower alkylidene group.
(154) A benzoheterocyclic derivative of the formula [1 ] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(155) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(156) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(157) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1] ), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula: 
(R9 and p are the same as defined above in the formula [1], and R8 is a lower alkoxy group).
(158) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a hydrogen atom.
(159) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a hydroxy group.
(160) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a carboxy-substituted lower alkyl group.
(161) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(162) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(163) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a lower alkanoyl group.
(164) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form an oxo group.
(165) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a lower alkylidene group.
(166) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(167) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(168) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(169) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a 9-oxofluorenyl group.
(170) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a hydrogen atom.
(171) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a hydroxy group.
(172) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a carboxy-substituted lower alkyl group.
(173) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(174) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(175) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a lower alkanoyl group.
(176) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form an oxo group.
(177) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a lower alkylidene group.
(178) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(179) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(180) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
(181) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: xe2x80x94C(R2)(R3)xe2x80x94Xxe2x80x94, X is a group of the formula: xe2x80x94NR14xe2x80x94 (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: xe2x80x94NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a 9-oxofluorenyl group.
(182) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a hydrogen atom.
(183) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a hydroxy group.
(184) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a carboxy-substituted lower alkyl group.
(185) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.
(186) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.
(187) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a lower alkanoyl group.
(188) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form an oxo group.
(189) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a lower alkylidene group.
(190) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.
(191) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.
(192) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.
Each group in the above formula [1] specifically means the following groups.
The lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.
The lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, etc.
The halogen atom is fluorine atom, chlorine atom, bromine atom or iodine atom.
The lower alkanoyloxy group includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butyl-carbonyloxy, hexanoyloxy, and the like.
The lower alkanoyl group having optionally a halogen substituent includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally be substituted by 1 to 3 halogen atoms, for example, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionoyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl, 5,6-dibromohexanoyl, and the like.
The amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group being optionally substituted by 1 to 2 groups selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acetylaminomethoxy, 1-acetylaminoethoxy, 2-propionylaminoethoxy, 3-isopropionylaminopropoxy, 4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy, 6-hexanoylaminohexyloxy, formylaminomethoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminoproxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, (N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the like.
The amino group having optionally a lower alkyl substituent includes an amino group which may optionally be substituted by 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butyl amino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, and the like.
The lower alkoxycarbonyl-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarbonylmethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxycarbonylmethoxy, and the like.
The carboxy-substituted lower alkoxy group includes a carboxyalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, and the like.
The aminocarbonyl-lower alkoxy group having a lower alkyl substituent includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an aminocarbonyl group having 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, methylaminocarbonylmethoxy, 1-ethylaminocarbonylethoxy, 2-propylaminocarbonylethoxy, 3-isopropylaminocarbonylpropoxy, 4-butylaminocarbonylbutoxy, 5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy, dimethylaminocarbonylmethoxy, 3-diethylaminocarbonylpropoxy, diethylaminocarbonylmethoxy, (N-ethyl-N-propylamino)carbonylmethoxy, 2-(N-methyl-N-hexylamino)carbonylethoxy, and the like.
The benzoyl group having optionally a halogen substituent on the phenyl ring includes a benzoyl group having optionally 1 to 3 halogen substituents on the phenyl ring, for example, benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl, 3-fluorobenzoyl, 4-fluoro-benzoyl, 2-bromobenzoyl, 3-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 4-iodobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 3,4-difluorobenzoyl, 3,5-dibromobenzoyl, 3,4,5-trichlorobenzoyl, and the like.
The carboxy-substituted lower alkyl group includes a carboxylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxylpropyl, and the like.
The lower alkoxycarbonyl-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonylmethyl, 3-methoxycarbonypropyl, ethoxycarbonylmethyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl, 6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethyl, and the like.
The amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent includes a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 2-aminoacetyloxy, 3-aminopropionyloxy, 2-aminopropionyloxy, 4-aminobutyryloxy, 2,2-dimethyl-3-aminopropionyloxy, 5-aminopentanoyloxy, 6-aminohexanoyloxy, 2-methyl-3-aminopropionyloxy, 2-methylaminoacetyloxy, 3-ethylaminopropionyloxy, 2-propylaminopropionyloxy, 4-isopropylaminobutyryloxy, 4-butylaminobutyryloxy, 4-tert-butyaminobutyryloxy, 5-pentylaminopentanoyloxy, 6-hexylaminohexanoyloxyl, 2-dimethylaminoacetyloxy, 3-diethylaminopropionyloxy, 2-dimethylaminopropionyloxy, 2-(N-ethyl-N-propylamino)acetyloxy, 3-(N-methyl-N-hexylamino)propionyloxy, and the like.
The lower alkanoyl group includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, t-butylcarbonyl, hexanoyl, and the like.
The lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms, for example, methylidene, ethylidene, propylidene, isopropylidene, butylidene, pentylidene, hexylidene, and the like.
The lower alkoxycarbonyl-substituted lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, ethoxycarbonylmethylidene, 2-methoxycarbonylethylidene, 3-isopropoxycarbonylpropylidene, 2-propoxycarbonylisopropylidene, 4-butoxycarbonylbutylidene, 5-pentyloxycarbonylpentylidene, 6-hexyloxycarbonylhexylidene, and the like.
The lower alkoxy-substituted lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethylidene, 2-ethoxyethylidene, 3-propoxypropylidene, 2-isopropoxyisopropylidene, 4-butoxybutylidene, 5-pentyloxypentylidene, 6-hexyloxyhexylidene, and the like.
The phenyl-substituted lower alkylidene group includes a straight chain or branched chain alkylidene having 1 to 6 carbon atoms which is substituted by a phenyl group, for example, phenylmethylidene, 2-phenylethylidene, 3-phenylpropylidene, 2-phenylpropylidene, 4-phenylbutylidene, 5-phenylpentylidene, 6-phenylhexylidene, and the like.
The lower alkylene group includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene, etc.
The amino-substituted lower alkyl group having optionally a lower alkyl substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diethylaminoethyl, 2-dimethylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, and the like.
The 5- to 7-membered saturated heterocyclic group which is formed by binding R6 and R7 or RB and RC together with the adjacent nitrogen atom to which they bond with or without being intervening with another nitrogen atom or an oxygen atom, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, homopiperazinyl, and the like.
The above heterocyclic group having a substituent selected from a lower alkyl group and a phenyl-lower alkyl group includes the above mentioned heterocyclic groups having 1 to 3 sustituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 2 phenyl groups, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-ethylhomopiperazinyl, 4-methylhomopiperazinyl, 4-hexylpiperazinyl, 4-diphenylmethylpiperazinyl, 4-benzylpiperazinyl, 3-methyl-4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(1-phenylethyl)pyrrolidinyl, 4-(3-phenylpropyl)-piperidinyl, 3-(4-phenylbutyl)morpholino, 3-(5-phenylpentyl)piperidinyl, 4-(6-phenylhexyl)piperazinyl, and the like.
The above heterocyclic group substituted by a lower alkyl group includes the above mentioned heterocyclic groups being substituted by 1 to 3 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-methylhomopiperazinyl, 4-hexylpiperazinyl, and the like.
The phenyl group having optionally a lower alkyl substituent includes a phenyl group which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-propylphenyl, 4-butylphenyl, 2-pentylphenyl, 3-hexylphenyl, 3,4-dimethylphenyl, 3,4,5-trimethylphenyl, and the like.
The phenyl group having optionally a lower alkoxy substituent includes a phenyl group which may optionally have 1 to 3 straight chain or branched chain alkoxy substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-propoxyphenyl, 4-butoxyphenyl, 2-pentyloxyphenyl, 3-hexyloxyphenyl, 2,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 3,4,5-trimethoxyphenyl, and the like.
The pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring includes a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms and a pyridyl group on the pyridine ring, for example, pyridylcarbonyl, 2-phenylpyridylcarbonyl, 3-phenylpyridylcarbonyl, 4-phenylpyridylcarbonyl, 2-(2-methylphenyl)pyridylcarbonyl, 3-(2-ethylphenyl)pyridylcarbonyl, 4-(3-propylphenyl)-pyridylcarbonyl, 2-(4-butylphenyl)pyridylcarbonyl, 3-(2-pentylphenyl)pyridylcarbonyl, 4-(3-hexylphenyl)pyridylcarbonyl, 2-(3,4-dimethylphenyl)pyridylcarbonyl, 3-(3,4,5-trimethylphenyl)pyridylcarbonyl, 3-(2-pyridyl)pyridylcarbonyl, 2-(3-pyridyl)pyridylcarbonyl, 4-(4-pyridyl)pyridylcarbonyl, and the like.
The phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and said alkyl moiety having optionally a hydroxy substituent, and the phenyl ring may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a halogen atom, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, 2-chlorobenzyl, 2-(3-chlorophenyl)ethyl, 2-fluorobenzyl, 1-(4-chlorophenyl)ethyl, 3-(2-fluorophenyl)propyl, 4-(3-fluorophenyl)butyl, 5-(4-fluorophenyl)pentyl, 1,1-dimethyl-2-(2-bromophenyl)ethyl, 6-(3-bromophenyl)hexyl, 4-bromobenzyl, 2-(2-iodophenyl)ethyl, 1-(3-iodophenyl)ethyl, 3-(4-iodophenyl)propyl, 3,4-dichlorobenzyl, 3,5-dichlorobenzyl, 2,6-dichlorobenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 3,4-difluorobenzyl, 3,5-dibromobenzyl, 3,4,5-trichlorobenzyl, 3,5-dichloro-4-hydroxybenzyl, 3,5-dimethyl-4-hydroxybenzyl, 2-methoxy-3-chlorobenzyl, 2-methylbenzyl, 2-(2-methylphenyl)ethyl, 1-(3-methylphenyl)-ethyl, 3-(4-methylphenyl)propyl, 4-(2-ethylphenyl)butyl, 5-(3-propylphenyl)-pentyl, 6-(4-butylphenyl)hexyl, 2-(2-pentylphenyl)ethyl, 1-(3-hexylphenyl)ethyl, 3-(3,4-dimethylphenyl)propyl, 2-(3,4,5-trimethylphenyl)ethyl, (2-methyl-6-chlorophenyl)methyl, 3-phenyl-2-hydroxypropyl, 2-phenyl-2-hyd roxyethyl, 1-phenyl-1-hydroxymethyl, 3-(4-methylphenyl)-3-hydroxypropyl, 4-(3-chloro-phenyl)-4-hydroxybutyl, 5-(2-bromophenyl)-5-hydroxypentyl, 6-(4-fluoro-phenyl)-6-hydroxyhexyl, and the like.
The phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a phenoxy group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, phenoxymethyl, 2-phenoxyethyl, 1-phenoxyethyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxypropyl, (2-methylphenoxy)methyl, 2-(2-methylphenoxy)ethyl, 3-phenoxypropyl, 4-(3-methylphenoxy)butyl, 5-(2-ethylphenoxy)pentyl, 6-(3-propylphenoxy)hexyl, 4-(butylphenoxy)methyl, 2-(2-pentylphenoxy)ethyl, 1-(3-hexylphenoxy)ethyl, 3-(3,4-dimethylphenoxy)propyl, 2-(3,4,5-trimethylphenoxy)ethyl, and the like.
The phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the alkanoyl moiety includes a phenoxyalkanoyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms being substituted by 1 to 3 halogen atoms, an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, a nitro group, an amino group substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a halogen atom on the phenyl ring, and the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which may optionally have 1 to 3 halogen substituents, for example, 2-phenoxyacetyl, 2-phenoxypropionyl, 3-phenoxypropionyl, 2-phenoxybutyryl, 4-phenoxybutyryl, 2,2-dimethyl-3-phenoxypropionyl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, 2-(2-chlorophenoxy)-acetyl, 2-(3-chlorophenoxy)acetyl, 2-(4-chlorophenoxy)acetyl, 2-(2-fluorophenoxy)acetyl, 2-(3-fluorophenoxy)acetyl, 3-(4-fluorophenoxy)propionyl, 2-(2-bromophenoxy)propionyl, 4-(3-bromophenoxy)butyryl, 5-(4-bromophenoxy)-pentanoyl, 6-(2-iodophenoxy)hexanoyl, 2-(3-iodophenoxy)acetyl, 3-(4-iodophenoxy)propionyl, 4-(3,4-dichlorophenoxy)butyryl, 2-(3,4-dichlorophenoxy)-acetyl, 2-(2,6-dichlorophenoxy)acetyl, 2-(2,3-dichlorophenoxy)acetyl, 2-(2,4-dichlorophenoxy)acetyl, 2-(3,4-difluorophenoxy)acetyl, 3-(3,5-dibromo-phenoxy)propionoyl, 2-(3,4,5-trichlorophenoxy)acetyl, 2-(2-methylphenoxy)-acetyl, 2-(3-methylphenoxy)acetyl, 2-(4-methylphenoxy)acetyl, 3-(2-ethylphenoxy)propionyl, 2-(3-ethylphenoxy)propionyl, 4-(4-ethylphenoxy)butyryl, 5-(4-isopropylphenoxy)pentanoyl, 6-(3-butylphenoxy)hexanoyl, 3-(4-pentyl-phenoxy)propionyl, 2-(4-hexylphenoxy)acetyl, 2-(3,4-dimethylphenoxy)acetyl, 2-(3,4-diethylphenoxy)acetyl, 2-(2,4-dimethylphenoxy)acetyl, 2-(2,5-dimethyl-phenoxy)acetyl, 2-(2,6-dimethylphenoxy)acetyl, 2-(3,4,5-trimethylphenoxy)-acetyl, 2-(3-chloro-4-methylphenoxy)acetyl, 2-(3-dimethylaminophenoxy)-acetyl, 2-(3-nitrophenoxy)acetyl, 2-(2-methoxyphenoxy)acetyl, 2-(3-methoxyphenoxy)acetyl, 2-(4-methoxyphenoxy)acetyl, 2-(2-phenylphenoxy)acetyl, 2-(2-trifluoromethylphenoxy)acetyl, 3-(2-aminophenoxy)propionyl, 4-(4-ethylaminophenoxy)butyryl, 5-(2,3-dimethoxyphenoxy)pentanoyl, 6-(2,4,6-trimethoxyphenoxy)hexanoyl, 3-(2-ethoxyphenoxy)propionyl, 4-(3-propoxyphenoxy)-propionyl, 2-(4-butoxyphenoxy)acetyl, 3-(4-pentyloxyphenoxy)propionyl, 4-(4-hexyloxyphenoxy)butyryl, 3-(2-nitrophenoxy)propionyl, 4-(4-nitrophenoxy)-butyryl, 3-(3-phenylphenoxy)propionyl, 4-(4-phenylphenoxy)butyryl, 5-[3-(2,2,2-trichloroethyl)phenoxy]pentanoyl, 6-[4-(5-bromohexyl)phenoxy]hexanoyl, 2-(4-phenyl-2-methoxyphenoxy)acetyl, 2-(2-phenyl-4-methylphenoxy)acetyl, 2-(2,4,6-trinitrophenoxy)acetyl, 2-(2,4-dinitrophenoxy)acetyl, 2-(3-phenyl-2-dimethylaminophenoxy)acetyl, 2-phenoxy-2,2-difluoroacetyl, 3-(3-dimethylaminophenoxy)-3-bromopropionyl, 4-(3-nitrophenoxy)-3,4,4-trichlorobutyryl, 5-(2-methoxyphenoxy)-5-iodopentanoyl, 2-(2,6-dichlorophenoxy)-2-chloroacetyl, 2-(4-methylphenoxy)-2,2,-difluoroacetyl, 2-(2-phenylphenoxy)-2,2-difluoroacetyl, 6-(2-phenylphenoxy)-6-bromohexanoyl, 2-(2-acetylaminophenoxy)-acetyl, and the like.
The aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group includes an aminocarbonyl group which may optionally have 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a pyridyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, N-ethyl-N-(pyridylmethyl)aminocarbonyl, N-ethyl-N-benzylaminocarbonyl, benzylaminocarbonyl, (2-phenylethyl)aminocarbonyl, (1-phenylethyl)aminocarbonyl, (3-phenylpropyl)aminocarbonyl, (4-phenybutyl)aminocarbonyl, (5-phenylpentyl)aminocarbonyl, (6-phenylhexyl)aminocarbonyl, N-methyl-N-benzylaminocarbonyl, pyridylmethylaminocarbonyl, (2-pyridylethyl)aminocarbonyl, (3-pyridylpropyl)aminocarbonyl, (4-pyridylbutyl)aminocarbonyl, (5-pyridylpentyl)-aminocarbonyl, (6-pyridylhexyl)aminocarbonyl, N-(pyridylmethyl)-N-benzyl-aminocarbonyl, N-methyl-N-(pyridylmethyl)aminocarbonyl, and the like.
The benzoyl group having optionally a lower alkyl substituent on the phenyl ring includes a benzoyl group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-ethylbenzoyl, 3-propylbenzoyl, 4-butylbenzoyl, 2-pentylbenzoyl, 3-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, and the like.
The cycloalkyl group includes a cycloalkyl group having 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.
The lower alkylthio group includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like.
The phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, 2-phenylacetyl, 3-phenylpropionyl, 4-phenylbutyryl, 2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenylhexanoyl, 2-(2-methylphenyl)-acetyl, 2-(3-methylphenyl)acetyl, 2-(4-methylphenyl)acetyl, 3-(2-ethylphenyl)-propionyl, 2-(3-ethylphenyl)propionyl, 4-(4-ethylphenyl)butyryl, 5-(4-isopropylphenyl)pentanoyl, 6-(3-butylphenyl)hexanoyl, 3-(4-pentylphenyl)propionyl, 2-(4-hexylphenyl)acetyl, 2-(3,4-dimethylphenyl)acetyl, 2-(3,4-diethylphenyl)-acetyl, 2-(2,4-dimethylphenyl)acetyl, 2-(2,5-dimethylphenyl)acetyl, 2-(2,6-dimethylphenyl)acetyl, 2-(3,4,5-trimethylphenyl)acetyl, and the like.
The halogen-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxyl, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-bromopropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 5-bromohexyloxy, 5,6-dichlorohexyloxy, and the like.
The amino-substituted lower alkoxy group having optionally a lower alkyl substituent includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, ethylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-isopropylaminobutoxy, 4-butylaminobutoxy, 4-tert-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, 2-diethylaminoethoxy, 2-dimethylaminoethoxy, (N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the like.
The phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-susbstituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent includes a phenyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a hydroxy group, a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, a nitro group, an amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a phenyl group, and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3-methyl-phenyl, 4-methylphenyl, 2-ethylphenyl, 3-propylphenyl, 4-butylphenyl, 2-pentylphenyl, 3-hexylphenyl, 3,4-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 4-ethoxyphenyl, 3-propoxyphenyl, 4-propoxyphenyl, 4-butoxyphenyl, 2-pentyloxyphenyl, 3-hexyloxyphenyl, 2,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2,4-dihydroxyphenyl, 3,4-dihydroxyphenyl, 2,4,6-trihydroxyphenyl, 2-acetyloxyphenyl, 3-propionyloxyphenyl, 2-benzyloxyphenyl, 3-benzyloxyphenyl, 4-benzyloxyphenyl, 2-(2-phenylethoxy)phenyl, 3-(3-phenylpropoxy)phenyl, 4-(4-phenylbutoxy)phenyl, 3-(1-phenylethoxy)phenyl, 2-(5-phenylpentyloxy)phenyl, 3-(6-phenylhexyloxy)phenyl, 2,4-dibenzyloxyphenyl, 3,4-dibenzyloxyphenyl, 3,4,5-tribenzyloxyphenyl, 4-butyryloxyphenyl, 2-pentanoyloxyphenyl, 4-hexanoyloxyphenyl, 2,4-diacetyloxyphenyl, 2,6-diacetyloxyphenyl, 3,4,5-triacetyloxyphenyl, 2-trifluoromethoxyphenyl, 3-(2-chloroethoxy)phenyl, 2-(3-bromopropoxy)phenyl, 4-iodomethoxyphenyl, 2-(2,3-dichloropropoxy)phenyl, 3-(4-fluorobutoxy)phenyl, 4-(3-chloro-2-methylpropoxy)phenyl, 2-(5-bromo-hexyloxy)phenyl, 3-(5,6-dichlorohexyloxy)phenyl, 4-(2,2,2-trichloroethoxy)-phenyl, 2,4-bistrifluoromethoxyphenyl, 2,4,6-tri(trifluoromethoxy)phenyl, 2-aminomethoxyphenyl, 3-(1-aminoethoxy)phenyl, 4-(3-aminopropoxy)phenyl, 2-(4-aminobutoxy)phenyl, 3-(5-aminopentyloxy)phenyl, 4-(6-aminohexyloxy)-phenyl, 2-methylaminomethoxyphenyl, 3-(2-propylaminoethoxy)phenyl, 2-(3-isopropylaminopropoxy)phenyl, 4-(4-butylaminobutoxy)phenyl, 2-(5-pentylaminopentyloxy)phenyl, 3-(6-hexylaminohexyloxy)phenyl, 4-dimethylaminomethoxyphenyl, 2-(N-ethyl-N-propylaminomethoxy)phenyl, 2-methyl-4-methoxyphenyl, 2-methyl-6-hydroxyphenyl, 4-methyl-2-(3-bromopropoxy)phenyl, 4-methoxy-2-(3-isopropylaminopropoxy)phenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2,3-dinitrophenyl, 2,4,6-trinitrophenyl, 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, 2,4-diaminophenyl, 3,4,5-triaminophenyl, 4-acetylaminophenyl, 2-propionylaminophenyl, 3-butyrylaminophenyl, 4-pentanoylaminophenyl, 4-hexanoylaminophenyl, 2,3-diacetylaminophenyl, 2,4,6-triacetylaminophenyl, and the like.
The anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes an anilino-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, anilinomethyl, 2-anilinoethyl, 1-anilinoethyl, 3-anilinopropyl, 4-anilinobutyl, 1,1-dimethyl-2-anilinoethyl, 5-anilinopentyl, 6-anilinohexyl, 2-methyl-3-anilinopropyl, (2-methylanilino)methyl, 2-(2-methylanilino)ethyl, 1-(3-methylanilino)-ethyl, 3-(4-methylanilino)propyl, 4-(2-ethylanilino)butyl, 5-(3-propylanilino)-pentyl, 6-(4-butylanilino)hexyl, 2-(2-pentylanilino)ethyl, 1-(3-hexylanilino)ethyl, 3-(3,4-dimethylanilino)propyl, 2-(3,4,5-trimethylanilino)ethyl, and the like.
The phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents selected from a halogen atom, a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, and an aminocarbonyl group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, phenylmethoxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, 2-methyl-3-phenylpropoxy, (2-chlorophenyl)methoxy, (2-bromophenyl)methoxy, 2-(4-fluorophenyl)ethoxy, 1-(4-bromophenyl)ethoxy, 3-(3-bromophenyl)propoxy, 4-(4-chlorophenyl)butoxy, 5-(2-iodophenyl)pentyloxy, 6-(3-iodophenyl)hexyloxy, (2,6-dichlorophenyl)methoxy, (2,3-dichlorophenyl)methoxy, (2,4-dichlorophenyl)methoxy, (3,4-difluorophenyl)methoxy, (3,4,5-trichlorophenyl)methoxy, (2-methoxycarbonylphenyl)methoxy, (3-ethoxycarbonylphenyl)methoxy, 2-(4-isopropoxycarbonylphenyl)ethoxy, 3-(2-butoxycarbonylphenyl)propoxy, 4-(3-pentyloxycarbonylphenyl)butoxy, 5-(4-hexyloxycarbonylphenyl)pentyloxy, 6-(2-methoxycarbonylphenyl)hexyloxy, (2,4-dimethoxycarbonylphenyl)methoxy, (2,4,6-triethoxycarbonylphenyl)methoxy, (2-carbamoylphenyl)methoxy, 2-(3-methylaminocarbonylphenyl)ethoxy, 1-(4-ethylaminocarbonylphenyl)ethoxy, 3-(2-isopropylaminocarbonylphenyl)propoxy, 4-(3-butylaminocarbonylphenyl)-butoxy, 5-(4-pentylaminocarbonylphenyl)pentyloxy, 6-(2-hexylaminocarbonylphenyl)hexyloxy, (2-dimethylaminocarbonylphenyl)methoxy, 2-(3-dibutylaminocarbonylphenyl)ethoxy, 1-(4-dihexylaminocarbonylphenyl)ethoxy, 3-[2-(N-ethyl-N-propylaminocarbonyl)phenyl]propoxy, (2-aminomethylaminocarbonylphenyl)methoxy, 2-[3-(2-aminoethylaminocarbonyl)phenyl]ethoxy, 3-[4-(3-aminopropylaminocarbonyl)phenyl]propoxy, 4-[2-(4-aminobutylaminocarbonyl)-phenyl]butoxy, 5-[3-(5-aminopentylaminocarbonyl)phenyl]pentyloxy, 6-[4-(6-aminohexylaminocarbonyl)phenyl]hexyloxy, [2-(N-methyl-N-methylaminomethyl)aminocarbonylphenyl]methoxy, 2-[3-(3-isopropylaminopropylaminocarbonyl)phenyl]ethoxy, 3-{4-[N-propyl-N-(5-pentylaminopentyl)aminocarbonyl]-phenyl}propoxy, {2-[N-methyl-N-(2-diethylaminoethyl)aminocarbonyl]phenyl}-methoxy, {2-[N,N-bis(diethylaminoethyl)aminocarbonyl]phenyl}methoxy, 4-[3-(N-ethyl-N-propylamino)methylaminocarbonylphenyl]butoxy, 5-[4-{N-[2-(N-methyl-N-hexylamino)ethyl]-N-ethylaminocarbonyl}phenyl]pentyloxy, 6-{4-chloro-2-[N-butyl-N-(6-hexylaminohexyl)aminocarbonyl]phenyl)hexyloxy, [2-bromo-4-(N-hexyl-N-dimethylaminomethyl)aminocarbonylphenyl]methoxy, (2-methoxycarbonyl-3-chlorophenyl)methoxy, and the like.
The benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring includes a benzoylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 halogen substituents on the phenyl ring, for example, benzoylmethoxy, 2-benzoylethoxy, 1-benzoylethoxy, 3-benzoylpropoxy, 4-benzoylbutoxy, 5-benzoylhexyloxy, 6-benzoylhexyloxy, 1,1-dimethyl-2-benzoylethoxy, 2-methyl-3-benzoylpropoxy, 2-(2-chlorobenzoyl)-ethoxy, 1-(3-chlorobenzoyl)ethoxy, (4-chlorobenzoyl)methoxy, 3-(2-fluorobenzoyl)propoxy, 4-(3-fluorobenzoyl)butoxy, 5-(4-fluorobenzoyl)pentyloxy, 6-(2-bromobenzoyl)hexyloxy, 1,1-dimethyl-2-(3-bromobenzoyl)ethoxy, 2-methyl-3-(4-bromobenzoyl)propoxy, (2-iodobenzoyl)methoxy, 2-(3-iodobenzoyl)-ethoxy, 3-(4-iodobenzoyl)propoxy, 4-(3,4-dichlorobenzoyl)butoxy, 5-(2,6-dichlorobenzoyl)pentyloxy, 6-(2,3-dichlorobenzoyl)hexyloxy, (2,4-dichlorobenzoyl)methoxy, (3,4-difluorobenzoyl)methoxy, (3,5-dibromobenzoyl)-methoxy, (3,4,5-trichlorobenzoyl)methoxy, and the like.
The phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, which is substituted by a phenyl group having optionally 1 to 3 halogen substituents on the phenyl ring, for example, styryl, 3-phenyl-2-propenyl, 3-phenyl-1-propenyl, 4-phenyl-3-butenyl, 4-phenyl-2-butenyl, 4-phenyl-1-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 5-phenyl-2-pentenyl, 5-phenyl-1-pentenyl, 1-methyl-3-phenyl-2-butenyl, 6-phenyl-5-hexenyl, 1-methylstyryl, 2-, 3- or 4-chlorostyryl, 3-(4-bromophenyl)-2-propenyl, 3-(3-fluorophenyl)-1-propenyl, 4-(4-iodophenyl)-3-butenyl, 5-(2-chlorophenyl)-4-pentenyl, 2-methyl-3-bromostyryl, 3,4-dichlorostyryl, 3,4,5-trichlorostyryl, and the like.
The benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 1,1-dimethyl-2-benzoylethyl, 5-benzoylpentyl, 6-benzoylhexyl, 2-methyl-3-benzoylpropyl, 2-(methylbenzoyl)-methyl, 2-(2-methylbenzoyl)ethyl, 1-(3-methylbenzoyl)ethyl, 3-(4-methylbenzoyl)propyl, 4-(2-ethylbenzoyl)butyl, 5-(3-propylbenzoyl)pentyl, 6-(4-butylbenzoyl)hexyl, 2-(2-pentylbenzoyl)ethyl, 1-(3-hexylbenzoyl)ethyl, 3-(3,4-dimethylbenzoyl)propyl, 2-(3,4,5-trimethylbenzoyl)ethyl, and the like.
The pyrrolidinyl-substituted lower alkoxy group includes a pyrrolidinylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrrolidinyl)methoxy, 2-(2-pyrrolidinyl)ethoxy, 1-(3-pyrrolidinyl)ethoxy, 3-(2-pyrrolidinyl)propoxy, 4-(3-pyrrolidinyl)butoxy, 5-(2-pyrrolidinyl)pentyloxy, 6-(3-pyrrolidinyl)hexyloxy, 1,1-dimethyl-2-(2-pyrrolidinyl)ethoxy, 2-methyl-3-(3-pyrrolidinyl)propoxy, 5-(1-pyrrolidinyl)pentyloxy, 2-(1-pyrrolidinyl)ethoxy, and the like.
The phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenyl-propyl, 2-methylbenzyl, 2-(2-methylphenyl)ethyl, 1-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 4-(2-ethylphenyl)butyl, 5-(3-propylphenyl)pentyl, 6-(4-butylphenyl)hexyl, 2-(2-pentylphenyl)ethyl, 1-(3-hexylphenyl)ethyl, 3-(3,4-dimethylphenyl)propyl, 2-(3,4,5-trimethylphenyl)ethyl, (2-methyl-6-chloro-phenyl)methyl, and the like.
The lower alkoxycarbonyl group includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyoxycarbonyl, and the like.
The aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent includes an aminocarbonyl group which may optionally have 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, aminomethylaminocarbonyl, 2-aminoethylaminocarbonyl, 1-aminoethylaminocarbonyl, 3-aminopropylaminocarbonyl, 4-aminobutylaminocarbonyl, 5-aminopentylaminocarbonyl, 6-aminohexylaminocarbonyl, 1,1-dimethyl-2-aminoethylaminocarbonyl, 2-methyl-3-aminopropylaminocarbonyl, methylaminomethylaminocarbonyl, 1-ethylaminoethylaminocarbonyl, 2-propylaminoethylaminocarbonyl, 3-isopropylaminopropylaminocarbonyl, 4-butylaminobutylaminocarbonyl, 5-pentylaminopentylaminocarbonyl, 6-hexylaminohexylaminocarbonyl, dimethylaminomethylaminocarbonyl, 2-diethylaminoethylaminocarbonyl, 2-dimethylaminoethylaminocarbonyl, (N-ethyl-N-propylamino)methylaminocarbonyl, 2-(N-methyl-N-hexylamino)ethylaminocarbonyl, N-methyl-N-(2-diethylaminoethyl)aminocarbonyl, N-ethyl-N-(methylaminomethyl)aminocarbonyl, and the like.
The lower alkyl group having optionally a hydroxy substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, and the like.
The carbamoyl-lower alkyl group includes a carbamoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl, 5-carbamoylpentyl, 6-carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylpropyl, and the like.
The adamantyl-substituted lower alkyl group includes an adamantyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, adamantylmethyl, 2-adamantylethyl, 1-adamantylethyl, 3-adamantylpropyl, 4-adamantylbutyl, 5-adamantylpentyl, 6-adamantylhexyl, 1,1-dimethyl-2-adamantylethyl, 2-methyl-3-adamantylpropyl, and the like.
The lower alkylsulfonyl group includes an alkylsulfonyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, and the like.
The hydroxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, and the like.
The phenyl-lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by 1 to 2 phenyl groups, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, diphenylmethyl, 2,2-diphenylethyl, and the like.
The quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring includes, for example, quinolylcarbonyl, 2-phenylquinolylcarbonyl, 3-phenylquinolylcarbonyl, 4-phenylquinolylcarbonyl, 5-phenylquinolylcarbonyl, 6-phenylquinolylcarbonyl, 7-phenylquinolylcarbonyl, 8-phenylquinolylcarbonyl, and the like.
The thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring includes, for example, thienylcarbonyl, 2-phenylthienylcarbonyl, 3-phenylthienylcarbonyl, 4-phenylthienylcarbonyl, and the like.
The thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring includes, for example, thiazolylcarbonyl, 2-phenylthiazolylcarbonyl, 4-phenylthiazolylcarbonyl, 5-phenylthiazolylcarbonyl, and the like.
The cycloalkylcarbonyl group includes a cycloalkylcarbonyl group having 3 to 8 carbon atoms in the cycloalkyl moiety, for example, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, and the like.
The lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group includes a straight chain or ranched chain alkanoyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 substituents selected from a halogen atom and a hydroxy group, for example, in addition to the above-mentioned lower alkanoyl groups having optionally a halogen substituent, 2-hydroxyacetyl, 3-hydroxypropionyl, 2-hydroxypropionyl, 4-hydroxybutyryl, 5-hydroxypentanoyl, 6-hydroxyhexanoyl, 2,2-dimethyl-3-hydroxypropionyl, and the like.
The halogen-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-bromopropyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, and the like.
The amino group having optionally a lower alkyl substituent includes an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, amino, methyl amino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, and the like.
The lower alkoxycarbonyl group having optionally a halogen substituent includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, which may optionally have 1 to 3 halogen substituents, for example, in addition to the above-mentioned lower alkoxycarbonyl groups, trifluoromethoxycarbonyl, trichloromethoxycarbonyl, chloromethoxycarbonyl, bromomethoxycarbonyl, fluoromethoxycarbonyl, iodomethoxycarbonyl, difluoromethoxycarbonyl, dibromomethoxycarbonyl, 2-chloroethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 3-bromopropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxycarbonyl, 4-fluorobutoxycarbonyl, 5-chloropentyloxycarbonyl, 3-chloro-2-methylpropoxycarbonyl, 5-bromohexyloxycarbonyl, 5,6-dichlorohexyloxycarbonyl, and the like.
The lower alkoxy-substituted lower alkanoyl group includes an alkoxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms and the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, 2-methoxyacetyl, 3-methoxypropionyl, 2-ethoxyacetyl, 3-ethoxypropionyl, 4-ethoxybutyryl, 3-propoxypropionyl, 2-methoxypropionyl, 6-propoxyhexanoyl, 5-isopropoxypentanoyl, 2,2-dimethyl-3-butoxypropionyl, 2-methyl-3-tert-butoxypropionyl, 2-pentyloxyacetyl, 2-hexyloxyacetyl, and the like.
The lower alkanoyloxy-substituted lower alkanoyl group includes an alkanoyloxyalkanoyl group wherein the alkanoyl moieties are a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, 2-acetyloxyacetyl, 3-acetyloxypropionyl, 2-propionyloxyacetyl, 3-propionyloxypropionyl, 4-propionyloxybutyryl, 3-butyryloxypropionyl, 2-acetyloxypropionyl, 6-propionyloxyhexanoyl, 5-butyryloxypentanoyl, 2,2-dimethyl-3-butyryloxypropionyl, 2-pentanoyloxyacetyl, 2-hexanoyloxyacetyl, and the like.
The quinolyloxy-substituted alkanoyl group includes a quinolyloxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-quinolyloxyacetyl, 3-quinolyloxypropionyl, 2-quinolyloxypropionyl, 4-quinolyloxybutyryl, 2,2-dimethyl-3-quinolyloxypropionyl, 5-quinolyloxypentanoyl, 6-quinolyloxyhexanoyl, and the like.
The phenyl-lower alkoxycarbonyl group includes a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1,1-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.
The benzoyl-lower alkyl group includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, and the like.
The tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which is substituted by a tetrahydroquinolyloxy group having optionally 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and an oxo group on the quinoline ring, for example, 2-tetrahydroquinolyloxyacetyl, 3-tetrahydroquinolyloxypropionyl, 2-tetrahydroquinolyloxypropionyl, 4-tetrahydroquinolyloxybutyryl, 2,2-dimethyl-3-tetrahydroquinolyloxypropionyl, 5-tetrahydroquinolyloxypentanoyl, 6-tetrahydroquinolyloxyhexanoyl, 2-(1-methyltetrahydroquinolyloxy)acetyl, 2-(2-oxotetrahydroquinolyloxy)acetyl, 3-(2-ethyltetrahydroquinolyloxy)propionyl, 2-(3-propyltetrahydroquinolyloxy)propionyl, 4-(4-butyltetrahydroquinolyloxy)butyryl, 2,2-dimethyl-3-(5-pentyltetrahydroquinolyloxy)propionyl, 5-(6-hexyltetrahydroquinolyloxy)pentanoyl, 6-(7-methyltetrahydroquinolyloxy)-hexanoyl, 2-(8-methyltetrahydroquinolyloxy)acetyl, 2-(1,4-dimethyltetrahydroquinolyloxy)acetyl, 2-(2,4,6-trimethyltetrahydroquinolyloxy)acetyl, 2-(1-methyl-2-oxotetrahydroquinolyloxy)acetyl, 3-(2-oxotetrahydroquinolyloxy)propionyl, 4-(2-oxotetrahydroquinolyloxy)butyryl, 5-(2-oxotetrahydroquinolyloxy)pentanoyl, 6-(2-oxotetrahydroquinolyloxy)hexanoyl, 2-(1,6-dimethyl-2-oxotetrahydroquinolyloxy)acetyl, and the like.
The tetrahydronaphthyloxy-lower alkanoyl group includes a tetrahydronaphthyloxyalkanoyl group wherein the alkanoyl group is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atom, for example, 2-tetrahydronaphthyloxyacetyl, 3-tetrahydronaphthyloxypropionyl, 2-tetrahydronaphthyloxypropionyl, 4-tetrahydronaphthyloxybutyryl, 2,2-dimethyl-3-tetrahydronaphthyloxypropionyl, 5-tetrahydronaphthyloxypentanoyl, 6-tetrahydronaphthyloxyhexanoyl, and the like.
The phenyl-lower alkenylcarbonyl group includes a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenyl moiety, for example cinnamoyl, 3-phenyl-2-propenylcarbonyl, 3-phenyl-1-propenylcarbonyl, 4-phenyl-3-butenylcarbonyl, 4-phenyl-2-butenylcarbonyl, 4-phenyl-1-butenylcarbonyl, 5-phenyl-4-pentenylcarbonyl, 5-phenyl-3-pentenylcarbonyl, 5-phenyl-2-pentenylcarbonyl, 5-phenyl-1-pentenylcarbonyl, 1-methyl-3-phenyl-2-butenylcarbonyl, 1-methylcinnamoyl, and the like.
The cycloalkenyl group includes a cycloalkenyl group having 3 to 8 carbon atoms, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like.
The phenyl-lower alkylaminocarbonyl group includes a phenylalkylaminocarbonyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzylaminocarbonyl, (2-phenylethyl)aminocarbonyl, (1-phenylethyl)aminocarbonyl, (3-phenylpropyl)aminocarbonyl, (4-phenylbutyl)aminocarbonyl, (5-phenylpentyl)aminocarbonyl, (6-phenylhexyl)aminocarbonyl, (1,1-dimethyl-2-phenylethyl)aminocarbonyl, (2-methyl-3-phenylpropyl)aminocarbonyl, and the like.
The 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyridyl, homopiperazinyl, 1,2,5,6-tetrahydropyridyl, thienyl, quinolyl, 1,4-dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, carbostyril, 3,4-dihydrocarbostyril, 1,2,3,4-tetrahydroquinolyl, indolyl, isoindolyl, indolinyl, benzimidazolyl, benzoxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, 1,2,3,4-tetrahydroquinolyl, 1,2-dihydroisoquinolyl, quinoxalinyl, cinnolinyl, phthalazinyl, 1,2,3,4-tetrazolyl, 1,2,4-triazolyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, imidazo[1,2-a]pyridyl, benzofuryl, 2,3-dihydrobenzo[b]furyl, benzothienyl, 1-azacycloheptyl, 4H-chromenyl, 1H-indazolyl, isoindolinyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, pyranyl, pyrazolidinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 1,4-benzothiadinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, tetrahydro-1,3-oxazinyl, tetrahydrooxazolyl, 1,4-dithianaphthalenyl, and the like.
The above-mentioned heterocyclic group having 1 to 3 substituents selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group includes the above-mentioned heterocyclic groups having 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a halogen atom, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and an oxo group, for example, 1-oxo-1,2,3,4-tetrahydroisoquinolyl, 2-oxo-piperidinyl, 2-oxo-1-azabicycloheptyl, 2-oxopyrrolidinyl, 5-phenylthiazolyl, 1-methylimidazolyl, 1-propylimidazolyl, 4-methylimidazolyl, 4-phenylimidazolyl, 1,4-dimethylpyrrolyl, 4-methylpiperazinyl, 4-phenylpiperidinyl, 4-methylthiazolyl, 2-oxothiazolyl, 5-ethylthiazolyl, 4-phenylthiazolyl, 4-propylthiazolyl, 5-butylthiazolyl, 4-pentylthiazolyl, 2-hexylthiazolyl, 4,5-dimethylthiazolyl, 5-phenyl-4-methylthiazolyl, 1-ethylimidazolyl, 4-propylimidazolyl, 5-butylimidazolyl, 1-pentylimidazolyl, 1-hexylimidazolyl, 1,4-dimethylimidazolyl, 1,4,5-trimethylimidazolyl, 1-phenylimidazolyl, 2-phenylimidazolyl, 5-phenylimidazolyl, 1-methyl-4-phenylimidazolyl, 3-methyl-1,2,4-triazolyl, 5-ethyl-1,2,4-triazolyl, 3-phenyl-1,2,4-triazolyl, 2-oxo-1-methylimidazolyl, 2-oxoimidazolyl, 2-ethylpyrrolyl, 3-propylpyrrolyl, 5-butylpyrrolyl, 4-pentylpyrrolyl, 2-hexylpyrrolyl, 2,4,5-trimethylpyrrolyl, 2-phenylpyrrolyl, 2,5-diphenylpyrrolyl, 2-methyl-5-phenylpyrrolyl, 2-oxopyrrolyl, 1-methyl-1,2,3,4-tetrazolyl, 1-phenyl-1,2,3,4-tetrazolyl, 1-ethyl-1,2,3,4-tetrazolyl, 1-propyl-1,2,3,4-tetrazolyl, 1-butyl-1,2,3,4-tetrazolyl, 1-pentyl-1,2,3,4-tetrazolyl, 1-hexyl-1,2,3,4-tetrazolyl, 1-phenyl-1,2,3,4-tetrazolyl, 2-methylpyridyl, 3-ethylpyridyl, 4-propylpyridyl, 2-butylpyridyl, 3-pentylpyridyl, 4-hexylpyridyl, 2-phenylpyridyl, 3-phenylpyridyl, 4-phenylpyridyl, 2,4-dimethylpyridyl, 2,4,6-trimethylpyridyl, 2-methyl-4-phenylpyridyl, 2,4-diphenylpyridyl, 2,4,6-triphenylpyridyl, 2-oxopyridyl, 4-oxopyridyl, 4-methyl-2-oxopyridyl, 2-phenyl-4-oxopyridyl, 3-methylimidazo[1,2-a]pyridyl, 4-ethylimidazo[1,2-a]pyridyl, 3-phenylimidazo[1,2-a]pyridyl, 5-phenylimidazo[1,2-a]-pyridyl, 3-methyl-1H-indazolyl, 3-phenyl-1H-indazolyl, 1-methyl-1,2,3,4-tetrahydroisoquinolyl, 5-ethyl-1,2,3,4-tetrahydroisoquinoly, 6-phenyl-1,2,3,4-tetrahydroisoquinolyl, 1-oxo-6-methyl-1,2,3,4-tetrahydroisoquinolyl, 1-oxo-7-phenyl-1,2,3,4-tetrahydroisoquinolyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 4-pentylmorpholino, 4-hexylpiperazinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, 3-methylthiomorpholino, 4-phenylpiperazinyl, 3-phenylpyrrolidinyl, 2-oxo-4-methylpiperidinyl, 2-oxo-3-methylpyrrolidinyl, 2-oxo-4-phenylpiperidinyl, 4-methyl-1-azabicycloheptyl, 5-phenyl-1-azacycloheptyl, 6-methyl-2-oxo-1-azacycloheptyl, 1-methyl-2-oxoimidazolidinyl, 1-isobutyl-2-oxoimidazolidinyl, 1-benzyl-2-oxoimidazolidinyl, 2-oxotetrahydro-1,3-oxazinyl, 3-phenyl-2-oxo-1-azacycloheptyl, 2-oxotetrahydrooxazolyl, 3-chloropyridyl, 4-methylpiperazinyl, 4-isobutylpiperazinyl, 4-methylhomopiperazinyl, 4-acetylpiperazinyl, 4-benzylpiperazinyl, 4-ethylhomopiperazinyl, and the like.
The cyano-substituted lower alkyl group includes a cyanoalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-2-cyanoethyl, 2-methyl-3-cyanopropyl, and the like.
The tetrazolyl-substituted lower alkyl group includes a tetrazolylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, tetrazolylmethyl, 2-tetrazolylethyl, 1-tetrazolylethyl, 3-tetrazolylpropyl, 4-tetrazolylbutyl, 5-tetrazolylpentyl, 6-tetrazolylhexyl, 1,1-dimethyl-2-tetrazolylethyl, 2-methyl-3-tetrazolylpropyl, and the like.
The lower alkanoyloxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyoxymethyl, 2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl, 4-acetyloxybutyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-acetyloxyhexyl, 6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and the like.
The amino group having optionally a lower alkanoyl substituent includes an amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.
The pyridyl-lower alkyl group includes a pyridylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (4-pyridyl)methyl, 1-(3-pyridyl)ethyl, 2-(2-pyridyl)-ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl, 5-(4-pyridyl)pentyl, 6-(2-pyridyl)-hexyl, 1,1-dimethyl-2-(3-pyridyl)ethyl, 2-methyl-3-(4-pyridyl)propyl, and the like.
The phenoxy-lower alkoxycarbonyl group includes a phenoxyalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, phenoxymethoxycarbonyl, 2-phenoxyethoxycarbonyl, 1-phenoxyethoxycarbonyl, 3-phenoxypropoxycarbonyl, 4-phenoxybutoxycarbonyl, 5-phenoxypentyloxycarbonyl, 6-phenoxyhexyloxycarbonyl, 1,1-dimethyl-2-phenoxyethoxycarbonyl, 2-methyl-3-phenoxypropoxycarbonyl, and the like.
The pyridyl-lower alkoxycarbonyl group includes a pyridylalkoxycarbonyl group wherein the alkoxycarbonyl group is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, (4-pyridyl)methoxycarbonyl, (2-pyridyl)methoxycarbonyl, (3-pyridyl)methoxycarbonyl, 2-(2-pyridyl)ethoxycarbonyl, 1-(1-pyridyl)ethoxycarbonyl, 3-(3-pyridyl)propoxycarbonyl, 4-(4-pyridyl)butoxycarbonyl, 5-(3-pyridyl)pentyloxycarbonyl, 6-(2-pyridyl)hexyloxycarbonyl, 1,1-dimethyl-2-(4-pyridyl)ethoxycarbonyl, 2-mehyl-3-(3-pyridyl)propoxycarbonyl, and the like.
The fluorenyl-lower alkoxycarbonyl group includes a fluorenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, (5-fluorenyl)methoxycarbonyl, 2-(2-fluorenyl)ethoxycarbonyl, 1-(1-fluorenyl)ethoxycarbonyl, 3-(3-fluorenyl)propoxycarbonyl, 4-(4-fluorenyl)butoxycarbonyl, 5-(5-fluorenyl)pentyloxycarbonyl, 6-(1-fluorenyl)-hexyloxycarbonyl, 1,1-dimethyl-2-(2-fluorenyl)ethoxycarbonyl, 2-methyl-3-(3-fluorenyl)propoxycarbonyl, and the like.
The lower alkenyloxycarbonyl group includes an alkenyloxycarbonyl group wherein the alkenyloxycarbonyl moiety is a straight chain or branched chain alkenyloxycarbonyl group having 2 to 6 carbon atoms in the alkenyloxy moiety, for example, vinyloxycarbonyl, allyloxycarbonyl, 2-butenyloxycarbonyl, 3-butenyloxycarbonyl, 1-methylallyloxycarbonyl, 2-pentenyloxycarbonyl, 2-hexenyloxycarbonyl.
The piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring includes a piperidinylalkoxycarbonyl group wherein the alkoxycarbonyl group is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, which may have optionally 1 to 3 substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (4-piperidinyl)methoxycarbonyl, 2-(3-piperidinyl)ethoxycarbonyl, 1-(2-piperidinyl)ethoxycarbonyl, 3-(1-piperidinyl)-propoxycarbonyl, 4-(4-piperidinyl)butoxycarbonyl, 5-(3-piperidinyl)pentyloxycarbonyl, 6-(2-piperidinyl)hexyloxycarbonyl, 1,1-dimethyl-2-(4-piperidinyl)-ethoxycarbonyl, 2-methyl-3-(1-piperidinyl)propoxycarbonyl, (1-ethyl-4-piperidinyl)methoxycarbonyl, (1-t-butoxycarbonyl-4-piperidinyl)methoxycarbonyl, (1-acetyl-4-piperidinyl)methoxycarbonyl, 2-(1-methyl-4-piperidinyl)ethoxycarbonyl, 1-(4-propyl-2-piperidinyl)ethoxycarbonyl, 3-(4-butyl-3-piperidinyl)propoxycarbonyl, 4-(3-pentyl-2-piperidinyl)butoxycarbonyl, 5-(1-hexyl-4-piperidinyl)pentyloxycarbonyl, (1,2-dimethyl-4-piperidinyl)methoxycarbonyl, (3,4,5-trimethyl-1-piperidinyl)methoxycarbonyl, 2-(1-methoxycarbonyl-4-piperidinyl)ethoxycarbonyl, 1-(1-ethoxycarbonyl-4-piperidinyl)ethoxycarbonyl, 3-(4-propoxycarbonyl-1-piperidinyl)propoxycarbonyl, 4-(3-pentyloxycarbonyl-2-piperidinyl)butoxycarbonyl, 5-(1-hexyloxycarbonyl-4-piperidinyl)-pentyloxycarbonyl, 6-(4-methoxycarbonyl-1-piperidinyl)hexyoxycarbonyl, 2-(2-acetyl-1-piperidinyl)ethoxycarbonyl, 1-(3-propionyl-2-piperidinyl)ethoxycarbonyl, 3-(4-butyryl-3-piperidinyl)propoxycarbonyl, 4-(4-pentanoyl-1-piperidinyl)butoxycarbonyl, 5-(1-hexanoyl-4-piperidinyl)pentyloxycarbonyl, 6-(1-acetyl-2-methyl-4-piperidinyl)hexyoxycarbonyl, (1-ethoxycarbonyl-2,6-dimethyl-4-piperidinyl)methoxycarbonyl, and the like.
The aminosulfonyloxy group having optionally a lower alkyl substituent includes an aminosulfonyloxy group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminosulfonyloxy, methylaminosulfonyloxy, ethylaminosulfonyloxy, propylaminosulfonyloxy, isopropylaminosulfonyloxy, butylaminosulfonyloxy, tert-butylaminosulfonyloxy, pentylaminosulfonyloxy, hexylaminosulfonyloxy, dimethylaminosulfonyloxy, diethylaminosulfonyloxy, dipropylaminosulfonyloxy, dibutylaminosulfonyloxy, dipentylaminosulfonyloxy, dihexylaminosulfonyloxy, N-methyl-N-ethylaminosulfonyloxy, N-ethyl-N-propylaminosulfonyloxy, N-methyl-N-butylaminosulfonyloxy, N-methyl-N-hexylaminosulfonyloxy, and the like.
The phenyl-lower alkyl group includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, and the like.
The lower alkanoyl-substituted amino group includes an amino group substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butycarbonylamino, hexanoylamino, and the like.
The benzoheterocyclic derivatives of the present invention can be prepared by the following processes. 
wherein G, R1, R2, R3, R and X are the same as defined above.
The process of Reaction Scheme-1 is carried out by reacting a benzoheterocyclic compound [2] and a carboxylic acid compound [3] by the conventional amido bond producing reaction. The amido bond producing reaction can be carried out under the conditions for the conventional amido bond producing reaction, for example,
(a) a mixed acid anhydride process, i.e. a process of reacting the carboxylic acid compound [3] with an alkyl carbonate to form a mixed acid anhydride and reacting the resultant with the amine compound [2],
(b) an activated ester process, i.e. a process of converting the carboxylic acid compound [3] into an activated ester such as p-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester, etc., and reacting the resultant with the amine compound [2],
(c) a carbodiimide process, i.e. a process of condensing the carboxylic acid compound [3] and the amine compound [2] in the presence of an activating agent such as dicyclohexylcarbodiimide, carbonyidiimidazole, etc.,
(d) other processes, i.e. a process of converting the carboxylic acid compound [3] into a carboxylic anhydride by treating it with a dehydrating agent such as acetic anhydride, and reacting the resultant with the amine compound [2]; a process of reacting an ester of the carboxylic acid compound [3] with a lower alcohol and the amine compound [2] at a high temperature under high pressure; a process of reacting an acid halide compound of the carboxylic acid compound [3], i.e. a carboxylic acid halide, with the amine compound [2], and the like.
The mixed acid anhydride used in the above mixed acid anhydride process (a) is obtained by the known Schxc3x6tten-Baumann reaction, and the reaction product is used without isolating from the reaction mixture for the reaction with the amine compound [2] to give the desired compound [1] of the present invention. The above Schxc3x6tten-Baumann reaction is usually carried out in the presence of a basic compound. The basic compound is any conventional compounds used in the Schxc3x6tten-Baumann reaction and includes, for example, organic basic compounds such as triethylamine, trimethylamine, pyridine, dimethylaniline, 1-methyl-2-pyrrolidine (NMP), N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), and inorganic basic compounds such as potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc. The reaction is usually carried out at a temperature from about xe2x88x9220xc2x0 C. to about 100xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 50xc2x0 C., for about 5 minutes to about 10 hours, preferably for 5 minutes to about 2 hours.
The reaction between the mixed acid anhydride thus obtained and the amine compound [2] is usually carried out at a temperature from xe2x88x9220xc2x0 C. to about 150xc2x0 C., preferably at a temperature from 10xc2x0 C. to about 50xc2x0 C., for 5 minutes to about 10 hours, preferably for 5 minutes to about 5 hours. The mixed acid anhydride process is usually carried out in a solvent. The solvent may be any conventional solvents which are usually used in the mixed acid anhydride process and includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, p-chlorobenzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, acetonitrile, hexamethylphosphoric triamide, etc.), or a mixture of these solvents. The alkyl halocarbonate used in the mixed acid anhydride process includes, for example, methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, isobutyl chloroformate, and the like. In said process, the carboxylic acid compound [3], the alkyl halocarbonate and the amine compound [2] are usually used in each equimolar amount, but preferably, the alkyl halocarbonate and the carboxylic acid compound [3] are used each in an amount of about 1 to 1.5 mole to 1 mole of the amine compound [2].
Among the above other processes (d), in case of the process of reacting the carboxylic acid halide with the amine compound [2], the reaction is usually carried out in the presence of a basic compound in an appropriate solvent. The basic compound is any conventional compounds and includes, for example, in addition to the basic compounds used in the above Schxc3x6tten-Baumann reaction, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, and the like. The solvent includes, for example, in addition to the solvents used in the mixed acid anhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), pyridine, acetone, water, and the like. The amount of the amine compound [2] and the carboxylic acid halide is not critical, but the carboxylic acid halide is usually used at least in equimolar amount, preferably about in an amount of 1 mole to 5 moles to 1 mole of the amine compound [2]. The reaction is usually carried out at a temperature from about xe2x88x9220xc2x0 C. to about 180xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 150xc2x0 C., for about 5 minutes to about 30 hours.
The amido bond producing reaction in above Reaction Scheme-1 may also be carried out by reacting the carboxylic acid compound [3] and the amine compound [2] in the presence of a condensing agent such as phosphorus compounds (e.g. phenylphosphine-2,2xe2x80x2-dithiodipyridine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric azide, bis(2-oxo-3-oxazolidinyl)phosphinic chloride, etc.).
The reaction is usually carried out in the presence of the solvent and the basic compound as used in the above reaction of the carboxylic acid halide and the amine compound [2] at a temperature from xe2x88x9220xc2x0 C. to 150xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 100xc2x0 C., for about 5 minutes to about 30 hours. The condensing agent and the carboxylic acid compound [3] are used at least in an equimolar amount, preferably in an amount of about 1 to 2 moles, to 1 mole of the amine compound [2]. 
wherein G, p, R1, R2, R3, R8 and X are the same as defined above, R10a is a hydrogen atom, a lower alkyl group or a lower alkanoyl group having optionally a halogen substituent, R11a is a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom, wherein the alkanoyl moiety may optionally be substituted by a halogen atom, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a group of the formula: 
a phenoxy-lower alkoxycarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, a lower alkoxycarbonyl group having optionally a halogen substituent, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a tetrahydroisoquinolylcarbonyl group, a phenyl-lower alkoxycarbonyl group or a phenyl-lower alkenylcarbonyl group, R11bis a lower alkyl group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, wherein the alkyl moiety may optionally be substituted by a hydroxy group, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a benzoyl-lower alkyl group or a lower alkylsulfonyl group, X1is a halogen atom, M is an alkali metal such as sodium, potassium, etc., and R15 is a lower alkyl group, a pyridyl-lower alkyl group or a phenyl-lower alkyl group.
The reaction of the compound [4] and the compound [5] is carried out in the same conditions as in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.
The reaction of the compound [4] and the compound [6a] is usually carried out in the presence or absence of a basic compound in an appropriate inert solvent. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, butanol, t-butanol, etc.), acetic acid, ethyl acetate, acetone, acetonitrile, pyridine, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, or a mixture of these solvents. The basic compound includes, for example, carbonates or hydrogen carbonates of alkali metal (e.g. sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, etc.), sodium hydride, potassium, sodium, sodium amide, metal alcoholates (e.g. sodium methylate, sodium ethylate, etc.), or organic basic compounds such as pyridine, N-ethyidiisopropylamine, dimethylaminopyridine, triethylamine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO). The amount of the compound [4] and the compound [6a] is not critical, but the compound [6a] is usually used at least in an equimolar amount, preferably in an amount of 1 to 10 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0xc2x0 C. to about 200xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 170xc2x0 C., for 30 minutes to about 75 hours. There may be added an alkali metal halide such as sodium iodide, potassium iodide, copper powder, etc. into the reaction system.
The reaction of the compound [4] and the compound [6b] is carried out under the same condition as in the reaction of the compound [1t] and the compound [18] in the following Reaction Scheme-9.
The reaction of the compound [4] and the compound [7] is carried out in the presence of an acid in an appropriate solvent. The acid includes, for example, organic acids (e.g. acetic acid, trifluoroacetic acid, etc.), or inorganic acids (e.g. hydrochloric acid, sulfuric acid, etc.). The solvent may be the same solvents as those used in the reaction of the carboxylic acid halide and the amine compound [2] in above Reaction Scheme-1. The compound [7] is used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is carried out at a temperature from 0xc2x0 C. to about 150xc2x0 C., preferably at a temperature from room temperature to about 100xc2x0 C., for 10 minutes to about 5 hours.
The reaction of the compound [4] and the compound [8] is carried out in the presence or absence of a basic compound, preferably in the absence of a basic compound, in an appropriate solvent or without a solvent. The solvent and the basic compound used therein are the same ones as those used in the reaction of the carboxylic acid halide and the amine compound [2] in above Reaction Scheme-1.
The compound [8] is usually used at least in an amount of 1 to 5 moles, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0xc2x0 C. to about 200xc2x0 C., preferably at a temperature from room temperature to 150xc2x0 C., for 5 minutes to about 30 hours. There may be added a boron compound such as boron trifluoride ethyl ether, etc. into the reaction system. 
wherein R1 and R are the same as defined above, Ga is a group of the formula: 
or a group of the formula: 
Gb is a group of the formula: 
or a group of the formula: 
Gc is a group of the formula: 
or a group of the formula: 
and X, Y, R4 and R5 are the same as defined above.
The reaction of converting the compound [1e] into the compound [1f] is carried out by reduction. The reduction reaction is carried out by using a hydrogenating agent. The hydrogenating agent includes, for example, lithium aluminum hydride, lithium borohydride, sodium borohydride, diboran, etc., and is used at least in an equimolar amount, preferably in an amount of 1 to 15 moles, to 1 mole of the starting compound. The reduction reaction is usually carried out in an appropriate solvent such as water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), or a mixture of these solvents. The reduction is usually carried out at a temperature from about xe2x88x9260xc2x0 C. to 150xc2x0 C., preferably at a temperature from xe2x88x9230xc2x0 C. to 100xc2x0 C., for about 10 minutes to 15 hours. When lithium aluminum hydride or diboran is used as a reducing agent, the reaction is preferably carried out in an anhydrous solvent such as tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.
The reaction of converting the compound [1e] into the compound [1g] is carried out in an appropriate solvent or without a solvent in the presence or absence of a dehydrating agent. The solvent includes, for example, alcohols (e.g. methanol, ethanol, isopropanol, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), aprotic polar solvents (e.g. dimethylformamide, dimethylacetamide, N-methylpyrrolidone, etc.), or a mixture of these solvents. The dehydrating agent includes, for example, drying agents which are conventionally used for drying solvents (e.g. molecular sieves, etc.), mineral acids (e.g. hydrochloric acid, sulfuric acid, boron trifluoride, etc.), organic acids (e.g. p-toluenesulfonic acid, acetic acid, etc.). The reaction is usually carried out at a temperature from room temperature to 250xc2x0 C., preferably at a temperature from bout 50xc2x0 C. to about 200xc2x0 C., for one to about 48 hours. The amount of the compound [9] is not critical, but it is used at least in an equimolar amount, preferably in an amount of 1 mole to excess amount, to 1 mole of the compound [1e]. The dehydrating agent is used in an excess amount when a drying agent is used, and when an acid is used as a dehydrating agent, it is used in a catalytic amount.
The subsequent reduction is carried out by various reduction reactions, for example, by catalytic hydrogenation in the presence of a catalyst in an appropriate solvent. The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran, diethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture of these solvents. The catalyst is, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 mole to 1 mole of the starting compound. The reaction is usually carried out at a temperature from xe2x88x9220xc2x0 C. to about 100xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 70xc2x0 C., under a pressure of 1 atm to 10 atms of hydrogen, or 0.5 hour to about 20 hours.
The above mentioned conditions for the reduction can be employed in the present reduction, but the reduction using a hydrogenating agent is more preferable. The hydrogenating agent includes, for example, lithium aluminum hydride, sodium borohydride, sodium cyanoborohydride, diboran, etc., and is used at least in an amount of 0.1 mole, preferably in an amount of 0.1 mole to 10 moles, to 1 mole of the compound [1e]. The reduction is carried out in an appropriate solvent such as water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diglyme, etc.), dimethylformamide, or a mixture of these solvents, at a temperature from about xe2x88x9260xc2x0 C. to about 50xc2x0 C., preferably at a temperature from xe2x88x9230xc2x0 C. to room temperature, for about 10 minutes to about 5 hours. When lithium aluminum hydride or diboran is used as a reducing agent, an anhydrous solvent such as diethyl ether, tetrahydrofuran, diglyme, etc., is preferably used. 
wherein R1, R and X1are the same as defined above, R5ais a lower alkyl group having optionally a hydroxy substituent, R16 and R17 are each a hydrogen atom or a lower alkyl group, R5bis a benzoyl group having optionally a halogen substituent on the phenyl ring, Gdis a group of the formula: 
or a group of the formula: 
Ge is a group of the formula: 
or a group of the formula: 
Gf is a group of the formula: 
or a group of the formula: 
R3a is a hydrogen atom or a hydroxy-substituted lower alkyl group, and X, Y, R4, R5a and R5b are the same as defined above.
The reaction of the compound [1h] and the compound [10] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6] in above Reaction Scheme-2.
The reaction of the compound [1h] and the compound [11] is carried out in the presence of a reducing agent in an appropriate solvent or without a solvent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetonitrile, formic acid, acetic acid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture thereof. The reducing agent includes, for example, formic acid, ammonium formate, alkali metal salts of fatty acids (e.g. sodium formate, etc.), hydrogenating agents (e.g. sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, etc.), catalysts (e.g. palladium-black, palladium-carbon, platinum oxide, platinum-black, Raney nickel, etc.), and the like.
When formic acid is used as a reducing agent, the reaction is usually carried out at a temperature from room temperature to about 200xc2x0 C., preferably at a temperature from about 50xc2x0 C. to about 150xc2x0 C., for about one to about 10 hours. Formic acid is used in an excess amount to the compound [1h].
When a hydrogenating agent is used, the reaction is usually carried out at a temperature from about xe2x88x9230xc2x0 C. to about 100xc2x0 C., preferably at a temperature from about 0xc2x0 C. to about 70xc2x0 C., for about 30 minutes to about 12 hours. The hydrogenating agent is used in an amount of 1 mole to 20 moles, preferably in an amount of 1 mole to 6 moles, to 1 mole of the compound [1h]. Especially, when lithium aluminum hydride is used as a reducing agent, the solvent is preferably ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, diglyme, etc.) or aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.).
Moreover, when a catalyst is used, the reaction is usually carried out under atmospheric pressure to 20 atms of hydrogen, preferably, under atmospheric pressure to 10 atms of hydrogen, or in the presence of a hydrogen donor such as formic acid, ammonium formate, cyclohexene, hydrazine hydrate, etc., at a temperature from xe2x88x9230xc2x0 C. to 100xc2x0 C., preferably at a temperature from 0xc2x0 C. to 60xc2x0 C., for about one to 12 hours. The catalyst is usually used in an amount of 0.1 to 40% by weight, preferably in an amount of 1 to 20% by weight to the amount of the compound [1h]. The hydrogen donor is usually used in an excess amount to the compound [1h].
The compound [11] is usually used at least in an equimolar amount, preferably in an amount of 1 mole to excess amount, to 1 mole of the compound [1h].
The reaction of the compound [1] and the compound [12] is carried out under the same conditions as those of the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1. 
wherein R1, R and X1 are the same as defined above, R18 is an amino-substituted lower alkanoyl group having optionally a lower alkyl substituent, a lower alkyl group, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: xe2x80x94ACONR6R7 (A, R6 and R7 are the same as defined above), Gg is a group of the formula: 
or a group of the formula: 
Gh is a group of the formula: 
or a group of the formula: 
X, Y and R3a are the same as defined above, R18xe2x80x2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent, a lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group or a group of the formula: xe2x80x94Oxe2x80x94ACONR6R7 (A, R6 and R7 are the same as defined above).
The reaction of the compound [1k] and the compound [13] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. 
wherein R1, R, X1 and Ga are the same as defined above, Gi is a group of the formula: 
or a group of the formula: 
X and Y are the same as defined above, R19 is a lower alkoxy group, R20 is a hydrogen atom, a lower alkoxycarbonyl group, a lower alkoxy group or a phenyl group, D is a lower alkylene group, n is 0 or 1, and R21 is a phenyl group.
The reaction of the compound [1e] and the compound [14] or the compound [15] is carried out in the presence of a basic compound in an appropriate solvent. The basic compound includes, for example, inorganic bases (e.g. sodium, potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc.), organic bases such as alkali metal alcoholates (e.g. sodium methylate, sodium ethylate, potassium t-butoxide, etc.), an alkyl lithium, aryl lithium or lithium amide (e.g. methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropyl amide, etc.), pyridine, piperidine, quinoline, triethylamine, N,N-dimethylaniline, and the like. The solvent may be any solvent which does not affect the reaction, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), and the like. The reaction is usually carried out at a temperature from xe2x88x9280xc2x0 C. to 150xc2x0 C., preferably at a temperature from xe2x88x9280xc2x0 C. to about 120xc2x0 C., for 0.5 to about 15 hours. 
wherein R1 and R are the same as defined above, Gj is a group of the formula: 
or a group of the formula: 
Gk is a group of the formula: 
or a group of the formula: 
Gl is a group of the formula: 
or a group of the formula: 
X, Y and D are the same as defined above, and R20a is a lower alkoxycarbonyl group.
The reaction of converting the compound [1n] into the compound [1o] is carried out under the same conditions as those in the reduction reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. When a hydrogenating agent is used in said reduction reaction, there may preferably be added a metal halide such as a nickel chloride into the reaction system.
The compound [1n] may be also converted into the compound [1o] by reducing the compound [1n] with metal magnesium-methanol. The reaction is usually carried out at a temperature from 0xc2x0 C. to 50xc2x0 C., preferably at a temperature from 0xc2x0 C. to room temperature, for one to about 10 hours. Metal magnesium is usually used in an amount of 1 to 10 moles, preferably in an amount of 1 to 7 moles, to 1 mole of the compound [1n]. When the compound [1n] wherein X is a methylene group is used in this reaction, there may be obtained the compound [1o] wherein X is a methylene group and the compound [1o] wherein X is a group of the formula:xe2x95x90CHxe2x80x94, but these compounds [1o] are easily separated.
The reaction of converting the compound [1o] into the compound [1p] is carried out in the presence or absence of an acid or a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.). The basic compounds includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature from room temperature to 200xc2x0 C., preferably at a temperature from room temperature to 150xc2x0 C., for 10 minutes to about 25 hours.
The compound [1p] is also prepared by treating the compound [1o] in an appropriate solvent in the presence of a dialkyl sulfide-Lewis acid such as dimethyl sulfide-aluminum chloride. The solvent may be the same solvents for the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. The reaction is usually carried out at a temperature from 0xc2x0 C. to 70xc2x0 C., preferably at a temperature from 0xc2x0 C. to 50xc2x0 C., for one to 10 hours. 
wherein R1 and R are the same as defined above, Gm is a group of the formula: 
or a group of the formula: 
Gn is a group of the formula: 
or a group of the formula: 
R22 s a carboxy-substituted lower alkyl group, and R3a, R6, R7, A, X and Y are the same as defined above.
The reaction of the compound [1q] and the compound [16] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1. 
wherein G, p, R1, R8, X1, A, m and R13 are the same as defined above, R9ais a benzoyl group having optionally a lower alkyl substituent on the phenyl ring, a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring or a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and R12a is a lower alkanoyl group.
The reaction of converting the compound [1s] into the compound [1t] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1f] in above Reaction Scheme-3.
The reaction of the compound [1t] and the compound [17] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.
The reaction of the compound [1t] and the compound [18] is carried out in the presence or absence of a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, the above-mentioned aromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol, etc.), dimethyl formamide, dimethyl sulfoxide, halogenated hydrocarbons (e.g. chloroform, methylene chloride, etc.), acetone, pyridine, and the like. The basic compound includes, for example, organic bases (e.g. triethylamine, pyridine, etc.), sodium hydroxide, potassium hydroxide, sodium hydride, and the like. The reaction is also carried out in the presence of a mineral acid (e.g. sulfuric acid, etc.) in a solvent such as acetic acid.
The compound [18] is used in an amount of 1 mole to excess amount, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from 0xc2x0 C. to about 200xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 150xc2x0 C., for 0.5 hour to about 20 hours.
The starting compound [2a] can be prepared by the processes as illustrated by the following Reaction Scheme. 
wherein G, p, R1 and R8 are the same as defined above.
The reaction of the compound [2] and the compound [19] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.
The reaction of converting the compound [20] into the compound [4] is carried out by (i) subjecting the compound [20] to reduction reaction by using a catalyst in an appropriate solvent, or (ii) subjecting the compound [20] to reduction reaction by using a mixture of a metal or a metal salt with an acid, a metal or a metal salt with an alkali metal hydroxide, a sulfide, an ammonium salt in an appropriate inert solvent.
When (i) a catalyst is used, the solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is used in an amount of 0.02 to 1 mole, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from xe2x88x9220xc2x0 C. to 150xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 100xc2x0 C., under a pressure of 1 to 10 atms of hydrogen, for 0.5 hour to 10 hours. There may be added an acid such as hydrochloric acid into the reaction system.
When the method (ii) is employed, there is used as a reducing agent a mixture of iron, zinc, tin or stannous chloride and a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or a mixture of iron, iron sulfide, zinc or tin and an alkali metal hydroxide (e.g. sodium hydroxide, etc.), a sulfide (e.g. ammonium sulfide, etc.), aqueous ammonia, an ammonium salt (e.g. ammonium chloride, etc.). The inert solvent includes, for example, water, acetic acid, methanol, ethanol, dioxane, and the like. The conditions for the above reduction can be selected according to the kinds of the reducing agent to be used. For example, when a mixture of stannous chloride and hydrochloric acid is used as a reducing agent, the reaction is preferably carried out at a temperature from 0xc2x0 C. to about 80xc2x0 C., for 0.5 hour to about 10 hours. The reducing agent may be used at least in an equimolar amount, usually in an amount of 1 to 5 moles, to 1 mole of the starting compound.
The starting compound [3] is prepared by the processes as illustrated by the following Reaction Schemes. 
wherein p, R8, D and X1 are the same as defined above, R24 is a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, X2 is a halogen atom, R23 is a lower alkoxycarbonyl group, R25 is a phenoxy group having optionally a lower alkyl substituent on the phenyl ring, R26 is a phenyl group having optionally a lower alkyl substituent on the phenyl ring, R27 is a phenyl-lower alkyl group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent, or a benzoyl-lower alkyl group having optionally a halogen substituent on the phenyl ring.
The reaction of the compound [21] and the compound [22] and the reaction of the compound [24] and the compound [27] are carried out in the presence of zinc and a catalyst in an appropriate solvent. The solvent includes, for example, ethers (e.g. 1,2-dimethoxyethane, diethyl ether, tetrahydrofuran, dioxane, etc.), acetonitrile, dimethylformamide, and the like. The catalyst includes, for example, palladium compounds or nickel compounds such as tetrakistriphenylphosphine palladium [Pd(PPh3)4], palladium acetate [Pd(OCOCH3)2], palladium chloride [PdCl2], bistriphenylphosphinenickel dichloride [Ni(PPh3)2Cl2], and the like. The reaction is usually carried out at a temperature from 0xc2x0 C. to 70xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 50xc2x0 C., for 1 hour to about 80 hours.
The compound [24] or the compound [27] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [21] or the compound [22], respectively. The catalyst is usually used in an amount of 0.01 to about 1 mole, preferably in an amount of 0.03 to about 0.3 mole, to 1 mole of the starting compound.
The reaction of the compound [24] and the compound [25] and the reaction of the compound [29] and the compound [30] are carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.
The reaction of converting the compound [23], [26], [28] or [31] into the compound [3a], [3b], [3c] or [3d], respectively, is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7. 
wherein R28 and R29 are each a lower alkyl group, R30 is a phenyl group having optionally a lower alkyl substituent on the phenyl ring, and p, R8 and X2 are the same as defined above.
The reaction of the compound [32] and the compound [33] is carried out in an appropriate solvent. The solvent may be any solvents used in Grignard reaction, but preferably ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), saturated hydrocarbons (e.g. pentane, hexane, heptane, cyclohexane, etc.), and the like. The compound [33] is usually used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [32]. The reaction is usually carried out at a temperature from xe2x88x9270xc2x0 C. to 50xc2x0 C., preferably at a temperature from xe2x88x9230xc2x0 C. to room temperature, for 1 to about 50 hours.
The reaction of converting the compound [34] into the compound [35] is carried out in the presence of an oxidizing agent in an appropriate solvent. The oxidizing agent includes, for example, chromic acid pyridinium salts (e.g. pyridinium chlorochromate, pyridinium dichlorochromate, etc.), dimethyl sulfoxide-oxazolyl chloride, dichromic acid, dichromates (e.g. sodium dichromate, potassium dichromate, etc.), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate, etc.), manganese dioxide, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and the like. The solvent used in the reaction with an oxidizing agent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenated hydrocarbons (e.g. chloroform, dichloromethane, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, dioxane, etc.), dimethylsulfoxide, dimethylformamide, or a mixture of these solvents. The oxidizing agent is usually used at least in an equimolar amount, preferably in an amount of 1 mole to 25 moles, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from about 0xc2x0 C. to about 100xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 70xc2x0 C., for 1 hour to about 7 hours.
The reaction of converting the compound [35] into the compound [3e] is carried out by subjecting the compound [35] to alkylation in the presence of an alkylating agent in an appropriate solvent, followed by subjecting the product to hydrolysis, or by subjecting directly the compound [35] to hydrolysis.
In the alkylation of the compound [35], the alkylating agent used therein includes, for example, an alkyl halide such as methyl iodide, etc. The alkylation reaction is usually carried out at a temperature from room temperature to about 200xc2x0 C., preferably at a temperature from room temperature to about 150xc2x0 C., for 1 hour to about 30 hours. The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethyl ether, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), polar solvents (e.g. dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, acetone, acetonitrile, nitromethane, etc.), and the like. The alkylating agent is usually used in an equimolar amount, preferably in an amount of 1 to 8 moles, to 1 mole of the compound [35].
The subsequent hydrolysis may be carried out by a conventional method, for example, by in the presence of a basic compound (e.g. sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide, etc.), or a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or an organic acid (e.g. acetic acid, etc.), in a solvent such as water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, ethylene glycol dimethyl ether, etc.), acetic acid, or a mixture of these solvents. The reaction is usually carried out at a temperature from room temperature to 200xc2x0 C., preferably at a temperature from room temperature to 150xc2x0 C., for 0.5 hour to 20 hours.
In the reaction of subjecting directly the compound [35] to hydrolysis, the reaction is carried out under the same conditions as those in the above hydrolysis. The reaction is carried out for 1 hour to 30 hours.
The compound [3e] is also prepared by subjecting the compound [35] to hydrolysis in the presence of a mineral acid (e.g. sulfuric acid, hydrochloric acid, nitric acid, etc.), or in the presence of an organic acid (e.g. acetic acid, aromatic sulfonic acid, etc.) under the same conditions such as solvents, reaction temperature, reaction period, as those in the above hydrolysis reaction.
The starting compound [32] is prepared by the processes as illustrated in the following Reaction Scheme. 
wherein p, R8, X2, R28, R29 and X2 are the same as defined above.
The reaction of the compound [36] and the compound [37] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The compound [37] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [36].
The reaction of the compound [38] and the compound [39] is carried out in a solvent such as ethers (e.g. diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), at a temperature from 0xc2x0 C. to 150xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 100xc2x0 C., for 0.5 hour to about 5 hours. The compound [39] is used at least in an equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole of the compound [38]. 
wherein p, R8, R23, R21 and X1 are the same as defined above, and R31 is a phenyl group having optionally a halogen substituent.
The reaction of the compound [39A] and the compound [40] is carried out under the same conditions as those in the reaction of the compound [1e] and the compound [14] or the compound [15] in above Reaction Scheme-6.
The reaction of converting the compound [41] into the compound [3f] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-6. 
wherein p, R8 and R23 are the same as defined above, R32 is a lower alkylsulfonyloxy group having optionally a halogen substituent, or a halogen atom, and R33 is a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a phenyl group and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent.
The reaction of the compound [42] and the compound [43] is carried out in an appropriate solvent in the presence or absence of a lithium compound such as lithium chloride, etc., in the presence of a basic compound and a catalyst. The solvent may be the same solvents as those used in the reaction of the compound [38] and the compound [39] in above Reaction Scheme-13. The basic compound may be the same basic compounds as those used in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The catalyst includes, for example, tetrakis(triphenylphosphine)palladium, palladium chloride, and the like. The reaction is usually carried out at a temperature from room temperature to 200xc2x0 C., preferably at a temperature from room temperature to about 150xc2x0 C., for one to about 10 hours. The basic compound and the lithium compound are each used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [42]. The catalyst is used in a catalytic amount.
The reaction of converting the compound [44] into the compound [3g] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7. 
wherein G, p, R1, R8 and R10a are the same as defined above, R11c is a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a benzoyl-lower alkyl group, or a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, R11d is in addition to the groups for R11c, a phenyl group having optionally a substituent selected from a lower alkyl group and a halogen atom.
The reaction of the compound [4] and the compound [45] is carried out in the presence of a dialkyl azodicarboxylate (e.g. diethyl azodicarboxylate, dibutyl diazodicarboxylate, etc.), a dialkyl azodicarboxyamide (e.g. 1,1xe2x80x2-azo-dicarbonyidi(piperidine), etc.), and a phosphorus compound e.g. a trialkylphosphine, a triarylphosphine, etc.). The solvent includes, for example, ethers (e.g. tetrahydrofuran, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), or a mixture of these solvents. The dialkyl azodicarboxylate, the phosphorus compound and the compound [45] are each used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from xe2x88x9220xc2x0 C. to 100xc2x0 C., preferably at a temperature from xe2x88x9220xc2x0 C. to 50xc2x0 C., for 1 hour to 30 hours.
The compound [1v] wherein R10a is a lower alkanoyl group having optionally a halogen substituent may be converted into the corresponding compound [1w] by subjecting the compound [1v] to hydrolysis. The hydrolysis is carried out under the same conditions as those in the hydrolysis of the compound [1] wherein R9 is a phenyl group having at least one lower alkanoyloxy substituent on the phenyl ring.
The reaction of the compound [4] and the compound [46] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. The compound [46] is used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. 
wherein G, p, R1, R8, X1 and X2 are the same as defined above.
The reaction of the compound [4a] and the compound [47] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. 
wherein G, p, R1, R8 and X1 are the same as defined above, and R34 is a lower alkyl group, a lower alkanoyl group, a phenyl-lower alkyl group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, or a pyrrolidinyl-substituted lower alkyl group.
The reaction of the compound [48] and the compound [49] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. 
wherein G, p, R1 and R8 are the same as defined above, and R35 is an anilino group having optionally a lower alkyl substituent on the phenyl ring.
The reaction of the compound [1A] and the compound [50] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. The compound [50] is used at least in an equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound [1A]. 
wherein R36 is a lower alkoxy group or a halogen atom, R37 is a lower alkyl group, R8, R28, R29, R9 and X2 are the same as defined above, and q is 0 or 1.
The reaction of the compound [51] and the compound [52] is carried out under the same conditions as those in the reaction of the compound [32] and the compound [33] in above Reaction Scheme-12. The compound [52] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [51]. 
wherein R8, p, R32 and R23 are the same as defined above, R38 is a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, or an amino-substituted lower alkoxy group having optionally a lower alkyl substituent, and r is 0, 1 or 2.
The reaction of the compound [54] and the compound [55] is carried out under the same conditions as those in the reaction of the compound [42] and the compound [43] in above Reaction Scheme-15.
The reaction of converting the compound [56] into the compound [3i] is carried out under the same conditions as those in the reaction of converting the compound [44] into the compound [3g] in above Reaction Scheme-15. 
wherein R28, R29, R8, p, X1and X2 are the same as defined above, s is an integer of 0 to 5, and R39xe2x80x2 is a lower alkyl group.
The reaction of the compound [32] and the compound [57] is carried out under the same conditions as those in the reaction of the compound [32] and the compound [33] in above Reaction Scheme-12.
The reaction of the compound [58] and the compound [59] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.
The reaction of the compound [38] and the compound [57] is carried out under the same conditions as those in the reaction of the compound [1e] and the compound [14] or the compound [15] in above Reaction Scheme-6. The compound [57] is used at least in an equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole of the compound [38].
The reaction of converting the compound [58] or the compound [60] into the compound [3j] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7, except the reaction is carried out for 1 hour to about 50 hours.
The reaction of converting the compound [3j] into the compound [3k] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. 
wherein R8, p and X2 are the same as defined above, R49 is a cyano group, a lower alkoxycarbonyl group or a carboxy group, R39 is a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl lower alkyl group, or an oxo group, and t is an integer of 0 to 3, and the group of the formula: 
is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom.
The reaction of the compound [61] and the compound [62] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.
When the compound [63] is a compound of the formula [63] wherein R49 is a cyano group or a lower alkoxycarbonyl group, the reaction of converting the compound [63] into the compound [3k] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7. 
wherein G, R1, R8, p and R10a are the same as defined above, R11e is a lower alkanoyl group having a halogen substituent, R40 is a phenyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a lower alkanoyl-substituted amino group, a nitro group and a halogen atom, a lower alkyl group, a lower alkanoyl group, a quinolyl group, a tetrahydroquinolyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, or a tetrahydronaphthyl group, R11f is a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a lower alkanoyl-substituted amino group, a nitro group and a halogen atom on the phenyl ring, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a quinolyloxy-substituted lower alkanoyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, or a tetrahydronaphthyloxy-substituted lower alkanoyl group.
The reaction of the compound [1C] and the compound [63] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.
The compound [1D] wherein R11f is a lower alkanoyloxy-substituted lower alkanoyl group is reacted under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7 to give the compound [1D] wherein the corresponding R11f is a lower alkanoyl group having a hydroxy substituent. 
wherein R1, G, R8, p and R10a are the same as defined above, and R49 is a tetrahydroisoquinolyl group or a group of the formula: 
The reaction of converting the compound [4] into the compound [1E] is carried out by (i) reacting the compound [4] with a carbonylating agent in the presence of a basic compound in an appropriate solvent, followed by (ii) reacting the resulting product with the compound [65] in the presence of a basic compound in an appropriate solvent.
The solvent and the basic compound used in the above process (i) may be each the same ones as those used in the reaction of reacting a carboxylic acid halide with the amine compound [2] in above Reaction Scheme-1. The carbonylating agent includes, for example, carbonyldiimidazole, phosgene, diphosgene, urea, triphosgene, etc. The carbonylating agent is usually used in an amount of 0.05 to 1 mole, preferably in an amount of 0.1 to 1 mole, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0xc2x0 C. to 200xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 180xc2x0 C., for 1 hour to about 10 hours.
The solvent and the basic compound used in the above process (ii) may be each the same ones as those used in the process (i). The processes (i) and (ii) are carried out in one-pot system. The compound [65] is used in an amount of 1 to 5 moles, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from room temperature to 150xc2x0 C., preferably at a temperature from room temperature to about 120xc2x0 C., for 0.5 hour to about 5 hours. 
wherein R1, R2, R3, R and X1 are the same as defined above, and RAxe2x80x2 is the same groups as those for RA other than a hydrogen atom.
The reaction of the compound [1F] and the compound [66] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. 
wherein R1, G, R8, p and X1 are the same as defined above.
The reaction of converting the compound [1H] into the compound [1I] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. 
wherein R1, G, R8, p and R10a are the same as defined above, R44 is a lower alkyl group having optionally a halogen substituent, a phenoxy-lower alkyl group, a phenyl-lower alkyl group, a pyridyl-lower alkyl group, a fluorenyl-lower alkyl group, a lower alkenyl group or a piperidinyl-lower alkyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring.
The reaction of converting the compound [4] into the compound [67] is carried out under the same conditions as those in the reaction of converting the compound [4] into the compound [1E] in above Reaction Scheme-25. 
wherein R1 and R are the same as defined above, Go is a group of the formula: 
or a group of the formula: 
Gp is a group of the formula: 
or a group of the formula: 
R3a, X and Y are the same as defined above, R45 is a cyano-substituted lower alkyl group, R46 is a tetrazolyl-substituted lower alkyl group, and M is an alkali metal such as sodium, potassium, etc.
The reaction of converting the compound [1K] into the compound [1L] is carried out by reacting the compound [1K] with the compound [68] in the presence of a basic compound in an appropriate solvent. The solvent includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. dioxane, diethylene glycol dimethyl ether, diethyl ether, tatrahydrofuran, etc.), polar solvents (e.g. dimethylformamide, dimethylacetamide, N-methylpyrrolidone, acetic anhydride, acetonitrile, dimethyl sulfoxide, hexamethylphosphoric triamide, etc.). The basic compound includes, for example, inorganic bases (e.g. sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium hydride, sodium, potassium, sodium amide, etc.), or organic bases (e.g. N,N-dimethylaniline, piperidine, pyridine, triethylamine, sodium acetate, potassium acetate, etc.). The compound [68] is used at least in an equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound [1K]. The reaction is usually carried out at a temperature from room temperature to 200xc2x0 C., preferably at a temperature from 50xc2x0 C. to about 150xc2x0 C., for 1 hour to about 40 hours. 
wherein R8, p, R9 and R23 are the same as defined above, R47 is a lower alkylsulfonyloxy group having optionally a halogen substituent, and R48 is a lower alkyl group.
The reaction of the compound [69], carbon monooxide [70] and the compound [71] is carried out in the presence of a catalyst and a basic compound in an appropriate solvent. The solvent and the basic compound used therein are the same ones as those used in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The catalyst includes, for example, palladium acetate, 1,3-bis(diphenylphosphino)propane (dppp), and the like. The reaction is usually carried out at a temperature from room temperature to 200xc2x0 C., preferably at a temperature from room temperature to about 150xc2x0 C., for 1 hour to about 10 hours. The compound [70], the compound [71] and the catalyst are each used in an excess amount to the compound [69]. 
wherein R50 is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group, and R32, R23, R8, p, X1 and X2 are the same as defined above.
The reaction of the compound [72] and the compound [73] is carried out under the same conditions as in the reaction of the compound [54] and the compound [55] in above Reaction Scheme-21.
The reaction of converting the compound [74] into the compound [3m] is carried out under the same conditions as in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.
The reaction of the compound [72] and the compound [75] is carried out under the same conditions as in the reaction of the compound [54] and the compound [55] in above Reaction Scheme-21.
The reaction of converting the compound [76] into the compound [3m] is carried out in the presence of a basic compound and an oxidizing agent in an appropriate solvent. The solvent and the oxidizing agent used therein are the same ones as those used in the reaction of converting the compound [34] into the compound [35] in above Reaction Scheme-12.
The basic compound includes, for example, sodium hydroxide, potassium hydroxide, sodium hydride, etc.
The oxidizing agent is used at least in an equimolar amount, preferably in an amount of 1 to 4 moles, to 1 mole of the compound [76].
The reaction is usually carried out at a temperature from 0xc2x0 C. to about 150xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 120xc2x0 C., for about 1 hour to about 7 hours.
The reaction of the compound [77] and the compound [78] is carried out by treating the compound [77] with a basic compound in an appropriate solvent, at a temperature from xe2x88x9280xc2x0 C. to 50xc2x0 C., preferably at a temperature from xe2x88x9280xc2x0 C. to room temperature, for 0.5 hour to 5 hours, and followed by reacting the product with the compound [78] in the presence of a zinc compound (e.g. zinc, zinc chloride, etc.), a catalyst and a basic compound in the same solvent.
The basic compound used for the treatment of the compound [77] includes an alkyl lithium, an aryl lithium, or a lithium amide, for example, methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropylamide, and the like. The basic compound is used at least in an quimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [77]. The solvent and the catalyst are the same as those in the reaction of the compound [21] and the compound [22] in above Reaction Scheme-11, and are used in the same amount as those in said reaction in above Reaction Scheme-11.
The reaction of the product derived from the compound [77] and the compound [78] is usually carried out at a temperature from 0xc2x0 C. to 150xc2x0 C., preferably at a temperature from 0xc2x0 C. to 100xc2x0 C., for 1 hour to about 10 hours.
The basic compound used in the reaction of the product derived from the compound [77] and the compound [78] includes, for example, in addition to diisopropylethylamine, the same basic compounds used in the reaction of a carboxylic acid halide of the compound [3] and the amine compound [2] in above Reaction Scheme-1.
The zinc compound and the basic compound used in the reaction of the product derived from the compound [77] and the compound [78] are used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [77].
The reaction of converting the compound [79] into the compound [74] is carried out by subjecting the compound [79] to catalytic hydrogenation in an appropriate solvent. The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethyl formamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 mole, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from xe2x88x9220xc2x0 C. to about 150xc2x0 C., preferably at a temperature from 0xc2x0 C. to about 100xc2x0 C., under 1 to 10 atms of hydrogen, for 0.5 hour to about 10 hours. There may be added sodium acetate, etc. into the reaction system. 
wherein R1, G, R8, p, X1, R39 and t are the same as defined above.
The reaction of the compound [80] and the compound [81] is carried our under the same conditions as in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. 
wherein R1, G, R8 and p are the same as defined above, and R51 and R52 are each a lower alkyl group.
The reaction of the compound [4a] and the compound [82] is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.).
The reaction is usually carried out at a temperature from room temperature to about 200xc2x0 C., preferably at a temperature from room temperature to about 150xc2x0 C., for 0.5 hour to about 5 hours. The compound [82] is used at least in an equimolar amount, preferably in an mount of 1 to 2 moles, to 1 mole of the compound [4a].
The compound of the formula [1] wherein R1 is a hydroxy group can be prepared by subjecting the compound of the formula [1] wherein R1 is a lower alkoxy group to de-alkylation. The de-alkylation reaction is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polar solvents (e.g. acetonitrile, etc.), organic acids (e.g. acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, potassium iodide, etc.), and a mixture of a Lewis acid and a iodide. The reaction is usually carried out at a temperature from room temperature to 150xc2x0 C., preferably at a temperature from room temperature to 120xc2x0 C., for 0.5 hour to 15 hours.
The compound of the formula [1] wherein R9 is a phenyl group having at least one phenyl-lower alkoxy substituent on the phenyl ring is converted into the compound of the formula [1] wherein R9 is a phenyl group having at least one hydroxy substituent on the phenyl ring by subjecting it to catalytic reduction. The catalytic reduction is carried out in the presence of a reducing agent in an appropriate solvent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetic acid, ethyl acetate, ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture of these solvents. The reducing agent includes, for example, catalysts such as palladium-black, palladium-carbon, platinum oxide, platinum-black, platinum-carbon, Raney nickel, etc. The reaction is usually carried out at a temperature from xe2x88x9230 to 100xc2x0 C., preferably at a temperature from 0xc2x0 C. to 60xc2x0 C., under a pressure from atmospheric pressure to 20 atms of hydrogen, preferably under a pressure from atmospheric pressure to 10 atms of hydrogen. The catalyst is usually used in an amount of 0.1 to 40% by weight, preferably in an amount of 0.1 to 20% by weight, to the amount of the starting compound.
The compound of the formula [1] wherein R9 is a phenyl group having at least one lower alkanoyloxy substituent on the phenyl ring, or a lower alkanoyloxy group can be converted into the compound of the formula [1] wherein R9 is a phenyl group having at least one hydroxy substituent on the phenyl ring or a hydroxy group, respectively, by subjecting them to hydrolysis. The hydrolysis is carried out in the presence of an acid or a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether etc.), fatty acids (e.g. formic acid, acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.), and the like. The basic compound includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature from room temperature to about 200xc2x0 C., preferably at a temperature from room temperature to about 150xc2x0 C., for 0.5 to about 25 hours.
The compound of the formula [1] wherein R8 is a lower alkoxy group can be converted into the compound of the formula [1] wherein R8 is a hydroxy group by subjecting it to de-alkylation reaction. The compound [1] wherein R9 is a phenyl group having at least one lower alkoxy substituent on the phenyl ring can be converted into the compound of the formula [1] wherein R9 is a phenyl group having at least one hydroxy substituent on the phenyl ring by subjecting it to de-alkylation reaction. The de-alkylation reaction is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polar solvents (e.g. acetonitrile, etc.), organic acids (e.g. acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, potassium iodide, etc.), and a mixture of a Lewis acid and a iodide. The reaction is usually carried out at a temperature from room temperature to 150xc2x0 C., preferably at a temperature from room temperature to 120xc2x0 C., for 0.5 hour to about 15 hours.
The compound of the formula [1] wherein R11 is a phenoxy-lower alkanoyl group having at least one amino substituent on the phenyl ring can be converted into the compound of the formula [1] wherein R11 is a phenoxy-lower alkanoyl group having at least one amino substituent having a lower alkyl substituent on the phenyl ring by reacting it with a compound of the formula: R41X1 [10a] (wherein R41 is a lower alkyl group and X1 is the same as defined above), or a compound of the formula: R16COR17 [1] (wherein R16 and R17 are the same as defined above) under the same conditions as those in the reaction of the compound [1h] and the compound [10] or the compound [11] in above Reaction Scheme-4.
The compound of the formula [1] wherein R9 is a 5- to 11-membered, saturated or unsaturate heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom wherein these heteroatoms may optionally be substituent, and said heterocyclic group has a secondary amino group on the heterocyclic nucleus, is reacted with a compound of the formula: R42X[10b] (wherein X is the same as defined above and R42 is a lower alkyl group, a phenyl-lower alkyl group or a lower alkanoyl group) or a group of the formula: R16COR17 [11] (wherein R16 and R17 are the same as defined above) under the same conditions as those in the reaction of the compound [1h] with the compound [10] or the compound [11] in above Reaction Scheme-4, to give the compound of the formula [1] wherein the corresponding R9 is the above heterocyclic group wherein the secondary amino group on the heterocyclic nucleus is substituted by a lower alkyl group, a phenyl-lower alkyl group or a lower alkanoyl group, or reacted with a compound of the formula: R43OH [12a] (wherein R43 is a lower alkanoyl group) under the same conditions as those in the reaction of the compound [2] with the compound [3] in above Reaction Scheme-1 to give the compound of the formula [1] wherein the corresponding R9 is a heterocyclic group wherein the secondary amino group on the heterocyclic nucleus is substituted by a lower alkanoyl group.
Among the desired compounds [1] of the present invention, the compounds having an acidic group can easily be converted into salts by treating with a pharmaceutically acceptable basic compound. The basic compound includes, for example, metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, etc.), alkali metal carbonates or hydrogen carbonates (e.g. sodium carbonate, sodium hydrogen carbonate, etc.) and alkali metal alcoholates (e.g. sodium methylate, potassium ethylate, etc.). Besides, among the desired compounds [1] of the present invention, the compounds having a basic group can easily be converted into acid addition salts thereof by treating with a pharmaceutically acceptable acid. The acid includes, for example, inorganic acids (e.g. sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, etc.), and organic acids (e.g. acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, citric acid, succinic acid, benzoic acid, etc.). These salts show as well excellent pharmacological activities as the desired compounds [1].
In addition, the compounds [1] of the present invention include stereoisomers and optical isomers, and these isomers are also useful as a vasopressin antagonist, vasopressin agonist or an oxytocin antagonist.
The compounds of the present invention thus obtained can easily be isolated and purified by conventional isolation methods. The isolation methods are, for example, distillation method, recrystallization method, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative thin layer chromatography, extraction with a solvent, and the like.
The desired compounds [1] of the present invention and salts thereof are useful as a vasopressin antagonist, vasopressin agonistic activities and an oxytocin antagonist, and are used in the form of a conventional pharmaceutical preparation. The preparation is prepared by using conventional diluents or carriers such as fillers, thickening agents, binders, wetting agent, disintegrators, surfactants, lubricants, and the like. The pharmaceutical preparations can be selected from various forms in accordance with the desired utilities, and the representative forms are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.), and the like. In order to form in tablets, there are used carriers such as vehicles (e.g. lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc.), binders (e.g. water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrators (e.g. dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose, etc.), disintegration inhibitors (e.g. white sugar, stearin, cacao butter, hydrogenated oils, etc.), absorption promoters (e.g. quaternary ammonium base, sodium laurylsulfate, etc.), wetting agents (e.g. glycerin, starches, etc.), adsorbents (e.g. starches, lactose, kaolin, bentonite, colloidal silicates, etc.), lubricants (e.g. purified talc, stearates, boric acid powder, polyethylene glycol, etc.), and the like. Moreover, the tablets may also be in the form of a conventional coated tablet, such as sugar-coated tablets, gelatin-coated tablets, enteric coated tablets, film coating tablets, or double or multiple layer tablets. in the preparation of pills, the carriers include vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc, etc.), binders (e.g. gum arabic powder, tragacanth powder, gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.), and the like. In the preparation of suppositories, the carriers include, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin, semi-synthetic glycerides, and the like. Capsules can be prepared by charging a mixture of the compound of the present invention and the above carriers into hard gelatin capsules or soft capsules in usual manner. In the preparation of injections, the solutions, emulsions and suspensions are sterilized and are preferably made isotonic with the blood. In the preparation of these solutions, emulsions and suspensions, there are used conventional diluents, such as water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, the pharmaceutical preparations may also be incorporated with sodium chloride, glucose, or glycerin in an amount sufficient to make them isotonic, and may also be incorporated with conventional solubilizers, buffers, anesthetizing agents. Besides, the pharmaceutical preparations may optionally be incorporated with coloring agents, preservatives, perfumes, flavors, sweeting agents, and other medicaments, if required.
The amount of the desired compound of the present invention to be incorporated into the vasopressin antagonist, vasopressin agonist or the oxytocin antagonist is not specified but may be selected from a broad range, but usually, it is preferably in the range of 1 to 70% by weight, more preferably 5 to 50% by weight.
The vasopressin antagonist, the vasopressin agonist or the oxytocin antagonist containing as an active ingredient the compounds [1] of the present invention or a salt thereof may be administered in any method, and a suitable method for administration may be determined in accordance with various forms of preparations, ages, sexes and other conditions of the patients, the degree of severity of diseases, and the like. For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. The injections are intravenously administered alone or together with a conventional auxiliary liquid (e.g. glucose, amino acid solutions), and further are optionally administered alone in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route, if required. Suppositories are administered in intrarectal route.
The dosage of the vasopressin antagonist, the vasopressin agonist and the oxytocin antagonist of the present invention may be selected in accordance with the usage, ages, sexes and other conditions of the patients, the degree of severity of the diseases, and the like, but it is usually in the range of about 0.6 to 50 mg of the active compound of the present invention per 1 kg of body weight of the patient per day. The active compound is preferably contained in an amount of about 10 to about 1000 mg per the dosage unit.